Genealogical method of study. The genealogical method as a universal method for studying human heredity What does the genealogical method study
The genealogical method is used to 1) obtain gene and genomic mutations 2) study the influence of upbringing on human ontogenesis 3) study the heredity and variability of a person 4) study the stages of evolution of the organic world
n n n The conclusion about the relationship of plants and animals can be made on the basis of 1) chromosome theory 2) the law of linked inheritance 3) gene theory 4) cell theory
n n n What organelle ensures the transport of substances in the cell? 1) chloroplast 2) mitochondrion 3) ribosome 4) endoplasmic reticulum
n n n What is typical for the somatic cells of vertebrates? 1) have a diploid set of chromosomes 2) form a zygote when merged 3) participate in sexual reproduction 4) have the same shape
The organism shown in the figure reproduces 1) by dividing in two 2) with the help of gametes 3) by budding 4) by spores
The intermediate nature of the inheritance of a trait is manifested in 1) linkage of genes 2) incomplete dominance 3) independent splitting 4) multiple action of genes
n What is the ratio of phenotypes in F 1 when crossing two yellow-grain pea plants (Aa)? n 1) 1: 1 n 2) 3: 1 n 3) 1: 1: 1 n 4) 9: 3: 1
n n n What type of variability is caused by a random combination of chromosomes during fertilization? 1) certain 2) phenotypic 3) mutational 4) combinative
n Which feature is similar in fungi and plants? n 1) the presence of chitin in the cell wall n 2) autotrophic nutrition n 3) unlimited growth n 4) the presence of a fruiting body
n n n Shoot - a vegetative organ formed by 1) a stem with leaves and buds 2) the top of the stem 3) internodes and nodes 4) rudimentary leaves
n n n Why are ferns classified as higher plants? 1) they live in a ground-air environment 2) their body consists of tissues and organs 3) their body is a cluster of cells - a thallus 4) in their development cycle, asexual generation is replaced by sexual
n n n Freshwater hydra is classified as Intestinal, as it 1) feeds on floating animals 2) has two layers of cells: ectoderm and endoderm 3) lives in fresh water 4) responds to irritants
n n n The peculiarity of the outer cover of reptiles is the presence of 1) a single-layer epidermis 2) horny scales 3) chitinous cover 4) skin glands
n n n The function of nutrient absorption in the human digestive system is performed by 1) muscle cells 2) epithelial cells 3) stomach glands 4) blood vessels
n n n The figure 4 indicates the articular 1) cavity 2) bag 3) head 4) cartilage layer
n n n Preparations prepared from weakened microbes or their poisons - 1) therapeutic sera 2) antibodies 3) vaccines 4) antibiotics
n n n The humoral function of the pancreas is manifested in the release into the blood of 1) glucose 2) insulin 3) adrenaline 4) thyroxine
n n n One of the causes of myopia is 1) a violation in the visual zone of the cerebral cortex 2) damage to the optic nerve 3) clouding of the lens 4) a decrease in the ability of the lens to change curvature
n n n The set of environmental factors in which individuals of a species live - criterion 1) ecological 2) geographical 3) physiological 4) morphological
n n n Genetic heterogeneity of individuals in a population is enhanced by 1) mutational variability 2) geographical isolation 3) struggle for existence 4) artificial selection
n n n The development of multicellular organisms from a zygote serves as evidence of 1) the origin of multicellular organisms from unicellular organisms 2) the adaptability of organisms to the environment 3) the individual development of plants and animals 4) the influence environment for the development of organisms
n n n Human atavisms include the appearance of 1) tail vertebrae 2) diaphragm 3) differentiated teeth 4) six-fingered limb
n n n Identify the organisms that enter into competitive relationships. 1) fungus and algae in lichen 2) cultivated and weeds 3) predator and prey 4) carnivores and herbivores
n n n The expansion of ozone holes is considered a global environmental problem, since 1) there is a decrease in substances from the biosphere 2) the temperature of the earth's surface rises 3) the gas composition of the atmosphere changes 4) more ultraviolet rays enter the biosphere
n n n What cell organelles contain a wide variety of enzymes involved in the breakdown of biopolymers to monomers? 1) in lysosomes 2) in ribosomes 3) in mitochondria 4) in chloroplasts
n n n total number. What is the percentage of nucleotides with cytosine in this molecule? 1) 30% 2) 40% 3) 60% 4) 80%
n n n Thanks to fertilization and meiosis 1) a constant number of chromosomes is maintained in generations 2) the likelihood of mutations in offspring is reduced 3) the number of chromosomes changes from generation to generation 4) the phenotype of individuals in populations of the species is preserved
n n n The frequency of linkage disorders between genes depends on 1) the structure of the chromosome 2) the distance between them 3) the number of linkage groups 4) the dominance or recessiveness of genes
n n n Interline hybridization in plant breeding contributes to 1) obtaining clean line 2) the manifestation of the effect of heterosis 3) the production of polyploids 4) the manifestation of mutant genes
n n n n How many species of plants are in the list: angiosperms, red clover, creeping clover, dicotyledons, legumes, cruciferous plants, common colza, wild radish, birch, lily of the valley? 1) 7 2) 2 3) 6 4) 4
n n n The similarity of nervous and muscular tissues lies in the fact that they have the Property 1) contractility 2) conduction 3) excitability 4) irritability
n n n The part of the visual analyzer that converts light stimuli into nerve impulses is 1) albuginea 2) rods and cones 3) visual cortex 4) vitreous body
n n n The highest concentration of living matter is observed 1) in the upper layers of the atmosphere 2) in the depths of the oceans 3) in the upper layers of the lithosphere 4) at the boundaries of three habitats
n n n n n Are the following statements about the evidence for evolution correct? A. In humans, at a certain stage of development, the tail section and gill slits are formed, which serve as paleontological evidence of evolution. B. Findings in Central Africa of primitive tools and human skeletal remains provide paleontological evidence for evolution. 1) only A is true 2) only B is true 3) both judgments are correct 4) both judgments are wrong
n n n n В 1 What processes occur in the prophase of the first division of meiosis? 1) formation of two nuclei 2) divergence of homologous chromosomes 3) formation of a metaphase plate 4) convergence of homologous chromosomes 5) exchange of sections of homologous chromosomes 6) spiralization of chromosomes
n n n n B 2 In insects with incomplete transformation 1) three stages of development 2) external fertilization 3) the larva is similar to an annelids 4) the larva is similar in external structure to the adult insect 5) the larva stage is followed by the pupal stage 6) the larva turns into an adult insect
n n n n n Q 3 What examples illustrate the achievement of biological progress in plants by aromorphoses? 1) the presence of double fertilization in flowering plants 2) the formation of roots in ferns 3) the reduction of evaporation by the formation of a wax coating on the leaves 4) the increased pubescence of leaves in angiosperms 5) the protection of seeds in fruits in angiosperms 6) the reduction of the vegetation period in plants growing in harsh climate
n n n n n Establish a correspondence between the sign of plants and the department to which they belong. SIGN OF PLANTS SECTION A) do not tolerate drought conditions B) life form - trees and shrubs C) the egg matures in the ovule D) form fine dry pollen E) there is a sprout in the development cycle 1) Ferns 2) Gymnosperms
n n n B 5 Match the function nervous system person and the department that performs this function. FUNCTION OF THE NERVOUS SYSTEM DEPARTMENT OF THE NERVOUS SYSTEM A) directs impulses to the skeletal muscles B) innervates the smooth muscles of organs C) ensures the movement of the body in space D) regulates the work of the heart E) regulates the work of the digestive glands 1) somatic 2) vegetative
n n n В 6 Establish a correspondence between the characteristics of the exchange and its type. CHARACTERISTICS TYPE OF METABOLISM A) oxidation of organic substances B) formation of polymers from monomers C) ATP breakdown D) energy storage in the cell E) DNA replication E) oxidative phosphorylation 1) plastic 2) energy
n n n n Establish a correspondence between the characteristics of organisms and the functional group to which they belong. CHARACTERISTICS OF ORGANISMS FUNCTIONAL GROUP A) are the first link in the food chain B) synthesize organic substances from inorganic C) use the energy of sunlight D) feed on ready-made organic substances E) return mineral substances to ecosystems E) decompose organic substances to mineral 1) producers 2) decomposers
n n n В 8 Indicate the sequence of processes of geographic speciation. 1) the spread of a trait in a population 2) the appearance of mutations in new living conditions 3) the spatial isolation of populations 4) the selection of individuals with beneficial changes
Using the picture, determine what form of selection it illustrates and under what conditions of life this selection will manifest itself. Will the size of the ears of hares change during evolution under the action of this form of natural selection? Justify the answer.
n n n C 3 What is the neurohumoral regulation of the work of the heart in the human body, what is its significance in the life of the body?
n n n C 4 Why is a mixed forest ecosystem considered more sustainable than a spruce forest ecosystem?
n n n C 5 What chromosome set is characteristic for the cells of the embryo and endosperm of the seed, leaves of a flowering plant. Explain the result in each case.
n n n C 6 When a pea plant with smooth seeds and tendrils was crossed with a plant with wrinkled seeds without tendrils, the whole generation was uniform and had smooth seeds and tendrils. When crossing another pair of plants with the same phenotypes (peas with smooth seeds and antennae and peas with wrinkled seeds without antennae), the offspring produced half of the plants with smooth seeds and antennae and half of the plants with wrinkled seeds without antennae. Make a diagram of each cross. Determine the genotypes of parents and offspring. Explain your results. How are dominant traits determined in this case?
3 hours (180 minutes) are allotted to complete the examination paper in biology. The work consists of 3 parts, including 50 tasks.
- Part 1 contains 36 tasks (A1-A36). Each question has 4 possible answers, only one of which is correct.
- Part 2 contains 8 tasks (B1-B8): 3 - with the choice of three correct answers out of six, 4 - for correspondence, 1 - for establishing the sequence of biological processes, phenomena, objects.
- Part 3 contains 6 tasks with a detailed answer (С1-С6).
All USE forms are filled in with bright black ink. The use of gel, capillary or fountain pens is allowed. When completing assignments, you can use a draft. Please note that entries in the draft will not be taken into account when evaluating the work.
We advise you to complete the tasks in the order in which they are given. To save time, skip the task that you can't complete right away and move on to the next one. If after completing all the work you have time left, you can return to the missed tasks.
The points you get for completed tasks are summed up. Try to complete as many tasks as possible and score the most points.
Part 1
When completing the tasks of this part in the answer sheet No. 1, under the number of the task you are performing (A1-A36), put the “×” sign in the box, the number of which corresponds to the number of the answer you have chosen.
A1 The genealogical method is used for
1) obtaining gene and genomic mutations
2) studying the influence of upbringing on human ontogenesis
3) studies of human heredity and variability
4) studying the stages of evolution of the organic world
A2 The conclusion about the relationship of plants and animals can be made on the basis of
1) chromosome theory
2) the law of linked inheritance
3) gene theory
4) cell theory
A3 What organelle provides transport of substances in the cell?
1) chloroplast
2) mitochondrion
3) ribosome
4) endoplasmic reticulum
A4 What is characteristic of the somatic cells of vertebrates?
1) have a diploid set of chromosomes
2) when merged, they form a zygote
3) participate in sexual reproduction
4) have the same shape
A5 Non-cellular life forms include
1) bacteriophages
2) cyanobacteria
3) protozoa
4) lichens
A6 The organism shown in the figure reproduces
1) dividing in two
2) with the help of gametes
3) budding
4) disputes
A7 The intermediate nature of the inheritance of a trait is manifested when
1) gene linkage
2) incomplete dominance
3) independent splitting
4) multiple action of genes
A8 What is the ratio of phenotypes in F1 when crossing two yellow-grained pea plants (Aa)?
1) 1: 1
2) 3: 1
3) 1: 1: 1: 1
4) 9: 3: 3: 1
A9 What type of variability is caused by a random combination of chromosomes during fertilization?
1) certain
2) phenotypic
3) mutational
4) combinative
A10 What feature is similar in fungi and plants?
1) the presence of chitin in the cell wall
2) autotrophic nutrition
3) unlimited growth
4) the presence of a fruiting body
A11 Shoot - a vegetative organ formed
1) stem with leaves and buds
2) the top of the stem
3) internodes and nodes
4) rudimentary leaves
A12 Why are ferns classified as higher plants?
1) they live in the ground-air environment
2) their body consists of tissues and organs
3) their body - a cluster of cells - thallus
4) in their development cycle, the asexual generation is replaced by the sexual
A13 Freshwater hydra belongs to the type Coelenterates, since it
1) eats swimming animals
2) has two layers of cells: ectoderm and endoderm
3) lives in fresh water
4) responds to the action of stimuli
A14 Feature of the outer cover of reptiles - the presence
1) single layer epidermis
2) horny scales
3) chitinous cover
4) skin glands
A15 The function of absorption of nutrients in the human digestive system is performed by
1) muscle cells
2) epithelial cells
3) stomach glands
4) blood vessels
A16 The number 4 indicates the articular
1) hollow
2) bag
3) head
4) layer of cartilage
A17 Preparations prepared from weakened microbes or their poisons -
1) therapeutic serums
2) antibodies
3) vaccines
4) antibiotics
A18 The humoral function of the pancreas is manifested in the release into the blood
1) glucose
2) insulin
3) adrenaline
4) thyroxine
A19 One of the causes of myopia is
1) violation in the visual zone of the cerebral cortex
2) damage to the optic nerve
3) clouding of the lens
4) a decrease in the ability of the lens to change curvature
A20 The set of environmental factors in which individuals of a species live is a criterion
1) ecological
2) geographical
3) physiological
4) morphological
A21 Genetic heterogeneity of individuals in a population is enhanced by
1) mutational variability
2) geographic isolation
3) struggle for existence
4) artificial selection
A22 The development of multicellular organisms from a zygote provides evidence
1) the origin of multicellular organisms from unicellular
2) adaptability of organisms to the environment
3) individual development of plants and animals
4) the influence of the environment on the development of organisms
A23 Human atavisms include the appearance
1) tail vertebrae
2) diaphragm
3) differentiated teeth
4) six-fingered limb
A24 Identify the organisms that enter into competitive relationships.
1) mushroom and algae in lichen
2) cultivated and weed plants
3) predator and prey
4) carnivores and herbivores
A25 What method of destruction of pests in agriculture and forestry belongs to the group of biological control methods?
A26 The expansion of ozone holes is considered a global environmental problem, since
1) there is a decrease in substances from the biosphere
2) the temperature of the earth's surface rises
3) the gas composition of the atmosphere changes
4) more ultraviolet rays enter the biosphere
A27 What organelles of the cell contain a wide variety of enzymes involved in the breakdown of biopolymers to monomers?
1) in lysosomes
2) in ribosomes
3) in mitochondria
4) in chloroplasts
A28 In a DNA molecule, the number of nucleotides with thymine is 20% of the total. What is the percentage of nucleotides with cytosine in this molecule?
1) 30%
2) 40%
3) 60%
4) 80%
A29 Due to fertilization and meiosis
1) a constant number of chromosomes is maintained in generations
2) the probability of manifestation of mutations in the offspring is reduced
3) the number of chromosomes changes from generation to generation
4) the phenotype of individuals is preserved in populations of the species
A30 Frequency of linkage disorder between genes depends on
1) chromosome structures
2) distances between them
3) the number of clutch groups
4) dominance or recessiveness of genes
A31 Interline hybridization in plant breeding promotes
1) getting a clean line
2) the manifestation of the effect of heterosis
3) obtaining polyploids
4) manifestation of mutant genes
A32 How many species of plants are in the list: angiosperms, red clover, creeping clover, dicotyledons, legumes, cruciferous plants, common colza, wild radish, birch, lily of the valley?
1) 7
2) 2
3) 6
4) 4
A33 The similarity of nervous and muscle tissues is that they have the property
1) contractility
2) conductivity
3) excitability
4) irritability
A34 The part of the visual analyzer that converts light stimuli into nerve impulses is
1) albuginea
2) rods and cones
3) visual cortex
4) vitreous body
A35 The highest concentration of living matter is observed
1) in the upper atmosphere
2) in the depths of the oceans
3) in the upper layers of the lithosphere
4) on the borders of three habitats
A36 Are the following statements about the evidence for evolution correct?
AND. In humans, at a certain stage of development, the tail section and gill slits are formed, which serves as paleontological evidence of evolution.
B. Findings in Central Africa of primitive tools and human skeletal remains serve as paleontological evidence of evolution.
1) only A is true
2) only B is true
3) both statements are correct
4) both judgments are wrong
Part 2
The answer to the tasks of this part (B1-B8) is a sequence of numbers. Write the answers first in the text of the work, and then transfer them to the answer sheet No. 1 to the right of the number of the corresponding task, starting from the first cell, without spaces, commas and other additional characters. Write each number in a separate cell in accordance with the samples given in the form.
In assignments B1-B3 choose three correct answers out of six. Circle the selected numbers and write them down in the table.
Q1 What processes occur in the prophase of the first division of meiosis?
1) the formation of two nuclei
2) divergence of homologous chromosomes
3) formation of a metaphase plate
4) convergence of homologous chromosomes
5) exchange of sections of homologous chromosomes
6) spiralization of chromosomes
B3 What examples illustrate the achievement of biological progress in plants by aromorphoses?
1) the presence of double fertilization in flowering plants
2) the formation of roots in ferns
3) reduction of evaporation by the formation of a wax coating on the leaves
4) increased pubescence of leaves in angiosperms
5) protection of seeds in fruits in angiosperms
6) reduction of the growing season in plants growing in a harsh climate
When performing tasks B4-B7 match the contents of the first and second columns. Enter the numbers of the selected answers in the table, and then transfer the resulting sequence of numbers to the answer form No. 1 without spaces or any symbols.
B4 Establish a correspondence between the sign of plants and the department to which they belong.
| AND | B | AT | G | D | E |
B7 Establish a correspondence between the characteristics of organisms and the functional group to which they belong.
| AND | B | AT | G | D | E |
In the task B8 establish the correct sequence of biological processes, phenomena, practical actions. Write down the numbers corresponding to them in the table, and then transfer the resulting sequence of numbers to the answer form No. 1 without spaces and any additional characters.
B8 Indicate the sequence of processes of geographic speciation.
1) the distribution of the trait in the population
2) the appearance of mutations in new living conditions
3) spatial isolation of populations
4) selection of individuals with beneficial changes
5) the formation of a new species
Don't forget to transfer all answers to the answer sheet No. 1.
Part 3
For answers to the tasks of this part (C1-C6), use the answer sheet No. 2. First write down the number of the task (C1, etc.), then the answer to it. For task C1, give a short free answer, and for tasks C2-C6 - a full detailed answer.
C1 What is the role of bacteria in the cycling of matter?
C2 
C3
C4
C5
C6
Assessment system for examination work in biology
Part 1
For the correct answer to each task of part 1, 1 point is put.
If two or more answers are given (including the correct one), an incorrect answer or no answer - 0 points.
job number | Answer | job number | Answer |
Part 2
Correctly completed tasks B1-B8 are evaluated as follows: 2 points - no errors; 1 point - one mistake was made; 0 points - two or more mistakes were made or there is no answer.
job number | Answer |
Part 3
CRITERIA FOR VERIFICATION AND EVALUATION OF THE PERFORMANCE OF TASKS WITH A DETAILED ANSWER
C1 What is the role of bacteria in the nutrient cycle?
Points |
|
Response elements: 1) heterotrophic bacteria - decomposers decompose organic substances into minerals that are absorbed by plants; 2) autotrophic bacteria (photo, chemotrophs) - producers | |
The answer includes 1 of the above items, OR the answer includes the 2 elements mentioned above, but contains non-gross biological errors | |
Wrong answer | |
Maximum score |
C2 Using the picture, determine what form of selection it illustrates and under what conditions of life this selection will manifest itself. Will the size of the ears of hares change during evolution under the action of this form of natural selection? Justify the answer.
Points |
|
Response elements: 1) a stabilizing form of selection, since the graph shows that 2) stabilizing selection manifests itself when relatively 3) changes in the size of the ears in hares in the process of evolution are not | |
The answer includes all the above elements, does not contain biological errors The answer includes all the above elements, does not contain biological errors | 3 |
The answer includes 2 of the above elements and does not contain | 2 |
The answer includes 1 of the above items and does not contain | 1 |
| Wrong answer | 0 |
| Maximum score | 3 |
C3 What is the neurohumoral regulation of the work of the heart in the human body, what is its significance in the life of the body?
Points |
|
Response elements: 1) nervous regulation is carried out due to the autonomic nervous 2) humoral regulation is carried out through the blood: adrenaline, 3) the nervous and endocrine systems provide self-regulation | |
The answer includes all the above elements and does not contain biological errors. | |
OR | |
OR | 1 |
| Wrong answer | 0 |
| Maximum score | 3 |
C4 Why is a mixed forest ecosystem considered more sustainable than a spruce forest ecosystem?
Points |
|
Response elements: 1) there are more species in a mixed forest than in a spruce forest; | |
The answer includes all the above elements, does not contain biological errors | |
The response includes 2 of the above elements and does not contain biological errors, OR the answer includes 3 of the above elements, but contains non-gross biological errors. | |
Wrong answer | |
Maximum score |
C5 What chromosome set is typical for the cells of the embryo and endosperm of the seed, leaves of a flowering plant. Explain the result in each case.
Points |
|
1) in the cells of the seed embryo, the diploid set of chromosomes is 2n, | |
The answer includes all the above elements, does not contain biological errors | |
The answer includes 2 of the above elements and does not contain biological errors, OR the answer includes 3 of the above elements, but contains non-gross biological errors. | |
The response includes 1 of the above elements and does not contain biological errors, OR the answer includes 2 of the above elements, but contains non-gross biological errors | |
Wrong answer | |
Maximum score |
C6 When a pea plant with smooth seeds and tendrils was crossed with a plant with wrinkled seeds without tendrils, the whole generation was uniform and had smooth seeds and tendrils. When crossing another pair of plants with the same phenotypes (peas with smooth seeds and antennae and peas with wrinkled seeds without antennae), the offspring produced half of the plants with smooth seeds and antennae and half of the plants with wrinkled seeds without antennae. Make a diagram of each cross. Determine the genotypes of parents and offspring. Explain your results. How are dominant traits determined in this case?
Points |
|||
The scheme for solving the problem includes: 1) 1st cross: R. AABB aabb 2) 2nd crossing: seeds smooth and tendrils x wrinkled and without tendrils R. AaBb aabb 3) The genes that determine smooth seeds and the presence of antennae are | |||
The answer includes all the above elements, does not contain biological errors | |||
The answer includes 2 of the above elements and does not contain biological errors, OR the answer includes the 3 elements mentioned above, but contains non-gross biological errors | |||
The answer includes 1 of the above elements and does not contain biological errors, OR the answer includes 2 of the above elements, but contains non-gross biological errors | |||
Wrong answer | |||
Maximum score |
Modern clinical medicine can no longer do without genetic methods. To study hereditary traits in humans, various biochemical, morphological, immunological, and electrophysiological methods are used. Thanks to the progress of genetic technologies, laboratory genetic diagnostic methods can be performed on a small amount of material that can be sent by mail (a few drops of blood on filter paper, or even on one cell taken at an early stage of development (N. P. Bochkov, 1999) (Fig. 1.118).
Rice. 1.118. M. P. Bochkov (born in 1931)
In solving genetic problems, the following methods are used: genealogical, twins, cytogenetic, somatic cell hybridization, molecular genetic, biochemical, dermatoglyphics and palmoscopy methods, population statistical, genome sequencing, etc.
Genealogical method for studying human heredity
The main method of genetic analysis in humans is to compile and study the pedigree.
Genealogy is genealogy. The genealogical method is the method of pedigrees, when a trait (disease) is traced in the family, indicating family ties between members of the pedigree. It is based on a thorough examination of family members, compilation and analysis of pedigrees.
This is the most universal method for studying human heredity. It is always used when a hereditary pathology is suspected, it allows you to establish in most patients:
The hereditary nature of the trait;
Type of inheritance and allele penetrance;
The nature of the linkage of genes and carry out the mapping of chromosomes;
The intensity of the mutation process;
Deciphering the mechanisms of gene interaction.
This method used in genetic counseling.
The essence of the genealogical method is to establish family ties, symptoms or disease among close and distant, direct and indirect relatives.
It consists of two stages: drawing up a pedigree and genealogical analysis. The study of the inheritance of a trait or disease in a particular family begins with the subject who has that trait or disease.
The individual that first comes to the attention of a geneticist is called a proband. It is predominantly a patient or a carrier of exploratory signs. Children of one parental couple are called sibs of the proband (brothers - sisters). Then they go to his parents, then to the brothers and sisters of the parents and their children, then to the grandparents, etc. When compiling a pedigree, make short notes about everyone from family members, his family ties with the proband. The pedigree scheme (Fig. 1.119) is accompanied by symbols under the figure and is called a legend.
Rice. 1.119. Pedigree of the family where cataract is inherited:
patients with this disease are family members I - 1, I And - 4, III - 4,
The use of the genealogical method made it possible to establish the nature of the inheritance of hemophilia, brachydactyly, achondroplasia, etc. It is widely used to clarify the genetic nature of the pathological condition and to predict the health of offspring.
Methods of compiling pedigrees, analysis. Drawing up a pedigree begins with a proband - a personwho turned to a geneticist or a doctor and contains a trait that needs to be studied in relatives on the paternal and maternal lines.
When compiling genealogical tables, they use the conventions proposed by G. Yust in 1931 (Fig. 1.120). Pedigree figures are placed horizontally (or along circle), one line every generation. On the left, each generation is designated in Roman numerals, and individuals in a generation are designated in Arabic from left to right and from top to bottom. Moreover, the oldest generation is placed on top of the pedigree and is indicated by the number i, and the smallest is at the bottom of the pedigree.
Rice. 1.120. Symbols that are used in the compilation of pedigrees.
Brothers and sisters in connection with the birth of the eldest are located on the left. Each member of the pedigree has its own code, for example, II - 4, II And - 7. The marriage couple of the pedigree is indicated by the same number, but with a small letter. If one of the spouses is not married, the information about it is not given at all. All individuals are placed strictly by generations. If the pedigree is great, then different generations are arranged not in horizontal rows, but in concentric ones.
After drawing up the pedigree, a written explanation is attached to it - the legend of the pedigree. The following information is reflected in the legend:
Results of clinical and post-clinical examination of the proband;
Information about the personal search of relatives proband;
Comparison of the results of the personal examination of the proband according to the survey of his relatives;
Written information about relatives living in another area;
Conclusion regarding the type of disease inheritance or traits.
When compiling a pedigree, one should not be limited only to a survey of relatives - this is not enough. Some of them prescribe a complete clinical, post-clinical or special genetic examination.
The purpose of genealogical analysis is to establish genetic patterns. Unlike other methods, a genealogical survey must be completed by a genetic analysis of its results. Analysis of the pedigree makes it possible to draw a conclusion regarding the nature of the trait (hereditary or not), title, inheritance (autosomal dominant, autosomal recessive or sex-linked), zygosity of the proband (homo - or heterozygous), degree of penetrance and expressivity of the gene under study
Features of pedigrees with different types of inheritance: autosomal dominant, autosomal recessive and article-linked. An analysis of pedigrees shows that all diseases determined by the mutant gene obey the classical laws Mendel for different types inheritance.
According to the autosomal dominant type of inheritance, dominant genes are phenotypically manifested in the heterozygous state and therefore their identification and the nature of inheritance does not cause difficulties.
1) one of the parents is sick in each affected person;
2) in an affected person who is married to a healthy woman, on average, half of the children are sick, and the other half are healthy;
3) healthy children of the affected parent have healthy children and grandchildren;
4) men and women are affected equally often;
5) the disease must manifest itself in every generation;
6) heterozygous individuals affected.
An example of an autosomal dominant type of inheritance may be the nature of the inheritance of six-fingered (large-fingered). Six-fingered limbs are a rather rare phenomenon, but are persistently preserved in many generations of some families (Fig. 1.121). Bagatopalia is consistently repeated in the offspring if at least one of the parents is bugatopalia, and is absent in those cases when the limbs are normal in both parents. In the offspring of rich-toed parents, this trait is present in equal numbers in boys and girls. The action of this gene in ontogenesis appears quite early and has a high penetrance.
Rice. 1.121. Genus with an autosomal dominant type of inheritance.
With autosomal dominant inheritance, the risk of developing the disease in offspring, regardless of gender, is 50%, but the manifestations of the disease to a certain extent depend on penetrance.
Analysis of pedigrees shows that syndactyly, Marfan's disease, achondroplasia, brachydactyly, Osler's hemorrhagic telangiectasia, hemachromatosis, hyperbilirubinemia, hyperlipoproteinemia, various dysostoses, marble disease, osteogenesis incomplete, Recklinghausen's neurofibromatosis, otosclerosis, Peltzius-Merzbacher's disease, pelginaemia leukocytes, periodic adynamia, pernicious anemia, polydactyly, acute intermittent porphyria, hereditary ptosis, idiopathic thrombocytopenic purpura, thalassemia, tuberous sclerosis, favism, Charcot-Marie disease, Sturge-Weber disease, multiple exostoses, lens ectopia, elliptocytosis (L. O. Badalyan et al., 1971).
According to autosomal recessive inheritance, recessive genes phenotypically appear only in the homozygous state, which makes it difficult to both identify and study the nature of inheritance.
This type of inheritance is characterized by the following patterns:
1) if a sick child was born to phenotypically normal parents, then the parents are necessarily heterozygotes;
2) if the affected sibs were born from a closely related marriage, then this is evidence of the recessive inheritance of the disease;
3) if they marry sick recessive disease and genotypic normal person, all their children will be heterozygous and phenotypically healthy;
4) if the marriage is ill and heterozygote, then half of their children will be affected, and half - heterozygous;
5) if two patients get married for the same recessive disease, then all their children will be sick.
6) men and women get sick with the same frequency:
7) heterozygotes are phenotypically normal, but are carriers of one copy of the mutant gene;
8) affected individuals are homozygous, and their parents are heterozygous carriers.
An analysis of pedigrees shows that the phenotype of the detection of recessive genes occurs only in those families where these genes have both parents at least in a heterozygous state (Fig. 1.122). Recessive genes in human populations remain undetected.
Rice. 1.122. Genus with an autosomal recessive type of inheritance.
However, in marriages between close relatives or in isolates (small groups of people), where marriages occur by close family ties, the expression of recessive genes increases. Under such conditions, the probability of a transition to a homozygous state and the phenotypic manifestation of rare recessive genes increases sharply.
Since most recessive genes have a negative biological significance and cause a decrease in vitality and the appearance of various virility and hereditary diseases, related marriages have a sharply negative character for the health of offspring.
Hereditary diseases are predominantly transmitted in an autosomal recessive manner, children from heterozygous parents can inherit diseases in 25% of cases (with complete penetrance). Given that complete penetrance is rare, the percentage of inheritance of the disease is also less.
По аутосомно-рецессивному типу наследуются: агаммаглобуліпемія, агранулоцитоз, алкаптонурія, альбинизм (рис. 1.123), амавротична идиотия, аміноацидурії, анемия аутоиммунная гемолитическая, анемия гипохромная мікроцитарна, анэнцефалия, галактоземия, гермафродитизм (рис 1.124), гепагоцеребральна дистрофия, болезнь Гоше, євнухоїдизм , myxedema, sickle cell anemia, fructosuria, color blindness(L. O. Badalyan et al., 1971).
Rice. 1.123. - Inheritance by autosomal recessive type. Albinism.
Rice. 1.124. Autosomal recessive inheritance. Hermaphroditism.
A number of diseases are inherited according to the X-chromosomal (sex-linked) type, when the mother is a carrier of the mutant gene, and half of her sons are sick. There are X-linked dominant X-linked recessive inheritance.
Genus of X-linked dominant inheritance (Fig. 1.125). This type of inheritance is characterized by:
1) Affected males pass on their disease to their daughters, but not to their sons;
2) affected heterozygous women transmit diseases to half of their children, regardless of their gender;
3) Affected homozygous females transmit the disease to all their children.
This type of inheritance is not common. The disease in women is not as severe as in men. It is rather difficult to distinguish between yourself X-linked dominant and autosomal dominant inheritance. The use of new technologies (DNA probes) helps to more accurately identify the type of inheritance.
Rice. 1.125. X-linked dominant inheritance.
Rodovid X-linked recessive inheritance (Fig. 1.126). This type is characterized by such inheritance patterns:
1) almost all affected are men;
2) the trait is transmitted through a heterozygous mother who is phenotypically healthy;
3) the affected father never transmits the disease to his sons;
4) all daughters of the sick father will be heterozygous carriers;
5) a carrier woman passes the disease on to half of her sons, none of the daughters will be sick, but half daughters - carriers of the hereditary gene.
Rice. 1.126. X-linked recessive inheritance.
More than 300 traits are caused by mutant genes located on the X chromosome.
An example of recessive inheritance of a sex-linked gene is hemophilia. The disease is relatively common in men and very rare in women. Phenotypically healthy women sometimes they are "carriers" and, when married to a healthy man, they give birth to sons with hemophilia. Such women are heterozygous for a gene that causes the loss of the ability to blood clot. From marriages of men with hemophilia to healthy women, healthy sons and carrier daughters are always born, and from marriages of healthy men to carrier women, half of the sons are sick and half of the daughters are carriers. As already noted, this is due to the fact that the father passes on his X chromosome to his daughters, and the sons receive from the father only Y -chromosome, which never contains the hemophilia gene, while their only X chromosome comes from the mother.
The following are the main diseases that are inherited in a recessive, sex-linked type.
Agammaglobulinemia, albinism (some forms), hypochromic anemia, Wiskott-Aldrich syndrome, Hutner syndrome, hemophilia A, hemophilia B, hyperparathyroidism, type VI glycogenosis, lack of glucose-6-phosphate dehydrogenase, nephrogenic non diabetes, ichthyosis, Lowe's syndrome, Peltzius-Merzbacher's disease, periodic paralysis, retinitis pigmentosa, pseudohypertrophic form of myopathy, Fabry's disease, phosphate diabetes, Scholz's disease, color blindness (Fig. 1.127).
Rice. 1.127. Test for determining color perception with Rabkin tables.
For genetic research, a person is an inconvenient object, since in a person: experimental crossing is impossible; a large number of chromosomes; puberty comes late; a small number of descendants in each family; equalization of living conditions for offspring is impossible.
A number of research methods are used in human genetics.
genealogical method
The use of this method is possible in the case when direct relatives are known - the ancestors of the owner of the hereditary trait ( proband) on the maternal and paternal lines in a number of generations or the descendants of the proband also in several generations. When compiling pedigrees in genetics, a certain system of notation is used. After compiling the pedigree, its analysis is carried out in order to establish the nature of the inheritance of the trait under study.
Conventions adopted in the preparation of pedigrees:
1 - man; 2 - woman; 3 - gender not clear; 4 - the owner of the studied trait; 5 - heterozygous carrier of the studied recessive gene; 6 - marriage; 7 - marriage of a man with two women; 8 - related marriage; 9 - parents, children and the order of their birth; 10 - dizygotic twins; 11 - monozygotic twins.
Thanks to the genealogical method, the types of inheritance of many traits in humans have been determined. So, according to the autosomal dominant type, polydactyly (an increased number of fingers), the ability to roll the tongue into a tube, brachydactyly (short fingers due to the absence of two phalanges on the fingers), freckles, early baldness, fused fingers, cleft lip, cleft palate, cataracts of the eyes, fragility of bones and many others. Albinism, red hair, susceptibility to polio, diabetes mellitus, congenital deafness, and other traits are inherited as autosomal recessive.
The dominant trait is the ability to roll the tongue into a tube (1) and its recessive allele is the absence of this ability (2).
3 - pedigree for polydactyly (autosomal dominant inheritance).
A number of traits are inherited sex-linked: X-linked inheritance - hemophilia, color blindness; Y-linked - hypertrichosis of the edge of the auricle, webbed toes. There are a number of genes located in homologous regions of the X and Y chromosomes, such as general color blindness.
The use of the genealogical method showed that in a related marriage, compared with an unrelated one, the likelihood of deformities, stillbirths, and early mortality in the offspring increases significantly. In related marriages, recessive genes often go into a homozygous state, as a result, certain anomalies develop. An example of this is the inheritance of hemophilia in the royal houses of Europe.
- hemophilic; - carrier woman
twin method
1 - monozygotic twins; 2 - dizygotic twins.
Children born at the same time are called twins. They are monozygotic(identical) and dizygotic(variegated).
Monozygotic twins develop from one zygote (1), which is divided into two (or more) parts during the crushing stage. Therefore, such twins are genetically identical and always of the same sex. Monozygotic twins are characterized by a high degree of similarity ( concordance) in many ways.
Dizygotic twins develop from two or more eggs that are simultaneously ovulated and fertilized by different spermatozoa (2). Therefore, they have different genotypes and can be either the same or different sex. Unlike monozygotic twins, dizygotic twins are characterized by discordance - dissimilarity in many ways. Data on the concordance of twins for some signs are given in the table.
| signs | Concordance, % | |
|---|---|---|
| Monozygotic twins | dizygotic twins | |
| Normal | ||
| Blood group (AB0) | 100 | 46 |
| eye color | 99,5 | 28 |
| Hair color | 97 | 23 |
| Pathological | ||
| Clubfoot | 32 | 3 |
| "Hare Lip" | 33 | 5 |
| Bronchial asthma | 19 | 4,8 |
| Measles | 98 | 94 |
| Tuberculosis | 37 | 15 |
| Epilepsy | 67 | 3 |
| Schizophrenia | 70 | 13 |
As can be seen from the table, the degree of concordance of monozygotic twins for all the above characteristics is significantly higher than that of dizygotic twins, but it is not absolute. As a rule, the discordance of monozygotic twins occurs as a result of intrauterine development disorders of one of them or under the influence of the external environment, if it was different.
Thanks to the twin method, a person's hereditary predisposition to a number of diseases was clarified: schizophrenia, epilepsy, diabetes mellitus and others.
Observations on monozygotic twins provide material for elucidating the role of heredity and environment in the development of traits. Moreover, the external environment is understood not only as physical factors of the environment, but also as social conditions.
Cytogenetic method
Based on the study of human chromosomes in normal and pathological conditions. Normally, a human karyotype includes 46 chromosomes - 22 pairs of autosomes and two sex chromosomes. The use of this method made it possible to identify a group of diseases associated either with a change in the number of chromosomes or with changes in their structure. Such diseases are called chromosomal.
Blood lymphocytes are the most common material for karyotypic analysis. Blood is taken in adults from a vein, in newborns - from a finger, earlobe or heel. Lymphocytes are cultivated in a special nutrient medium, which, in particular, contains substances that “force” lymphocytes to intensively divide by mitosis. After some time, colchicine is added to the cell culture. Colchicine stops mitosis at the metaphase level. It is during metaphase that the chromosomes are most condensed. Next, the cells are transferred to glass slides, dried and stained with various dyes. Coloring can be a) routine (chromosomes stain evenly), b) differential (chromosomes acquire transverse striation, with each chromosome having an individual pattern). Routine staining allows you to identify genomic mutations, determine the group belonging of the chromosome, and find out in which group the number of chromosomes has changed. Differential staining allows you to identify chromosomal mutations, determine the chromosome to the number, find out the type of chromosomal mutation.
In cases where it is necessary to conduct a karyotypic analysis of the fetus, cells of the amniotic (amniotic) fluid are taken for cultivation - a mixture of fibroblast-like and epithelial cells.
Chromosomal diseases include: Klinefelter syndrome, Turner-Shereshevsky syndrome, Down syndrome, Patau syndrome, Edwards syndrome and others.
Patients with Klinefelter's syndrome (47, XXY) are always male. They are characterized by underdevelopment of the sex glands, degeneration of the seminiferous tubules, often mental retardation, high growth (due to disproportionately long legs).
Turner-Shereshevsky syndrome (45, X0) is observed in women. It manifests itself in slowing down puberty, underdevelopment of the gonads, amenorrhea (absence of menstruation), infertility. Women with Turner-Shereshevsky syndrome are small in stature, the body is disproportionate - the upper body is more developed, the shoulders are wide, the pelvis is narrow - the lower limbs are shortened, the neck is short with folds, the “Mongoloid” eye shape and a number of other signs.
Down syndrome is one of the most common chromosomal diseases. It develops as a result of trisomy on chromosome 21 (47; 21, 21, 21). The disease is easily diagnosed, as it has a number of characteristic features: shortened limbs, a small skull, a flat, wide nose, narrow palpebral fissures with an oblique incision, the presence of a fold of the upper eyelid, and mental retardation. Violations of the structure of internal organs are often observed.
Chromosomal diseases also occur as a result of changes in the chromosomes themselves. Yes, deletion R-arm of autosome number 5 leads to the development of the "cat's cry" syndrome. In children with this syndrome, the structure of the larynx is disturbed, and in early childhood they have a kind of “meowing” voice timbre. In addition, there is a retardation of psychomotor development and dementia.
Most often, chromosomal diseases are the result of mutations that have occurred in the germ cells of one of the parents.
Biochemical method
Allows you to detect metabolic disorders caused by changes in genes and, as a result, changes in the activity of various enzymes. Hereditary metabolic diseases are divided into diseases of carbohydrate metabolism (diabetes mellitus), metabolism of amino acids, lipids, minerals, etc.
Phenylketonuria refers to diseases of amino acid metabolism. The conversion of the essential amino acid phenylalanine to tyrosine is blocked, while phenylalanine is converted to phenylpyruvic acid, which is excreted in the urine. The disease leads to the rapid development of dementia in children. Early diagnosis and diet can stop the development of the disease.
Population-statistical method
It is a method of studying the distribution of hereditary traits (inherited diseases) in populations. An essential point when using this method is the statistical processing of the obtained data. Under population understand a group of individuals of the same species, long time living in a certain territory, freely interbreeding with each other, having a common origin, a certain genetic structure and, to one degree or another, isolated from other such populations of individuals of a given species. A population is not only a form of existence of a species, but also a unit of evolution, since the basis of microevolutionary processes culminating in the formation of a species are genetic transformations in populations.
The study of the genetic structure of populations deals with a special section of genetics - population genetics. In humans, three types of populations are distinguished: 1) panmictic, 2) demes, 3) isolates, which differ from each other in number, frequency of intra-group marriages, the proportion of immigrants, and population growth. The population of a large city corresponds to the panmictic population. The genetic characteristics of any population includes the following indicators: 1) gene pool(the totality of genotypes of all individuals of a population), 2) gene frequencies, 3) genotype frequencies, 4) phenotype frequencies, marriage system, 5) factors that change gene frequencies.
To determine the frequencies of occurrence of certain genes and genotypes, hardy-weinberg law.
Hardy-Weinberg law
In an ideal population, from generation to generation, a strictly defined ratio of frequencies of dominant and recessive genes (1), as well as the ratio of frequencies of genotypic classes of individuals (2) is preserved.
p + q = 1, (1)R 2 + 2pq + q 2 = 1, (2)
where p— frequency of occurrence of the dominant gene A; q- the frequency of occurrence of the recessive gene a; R 2 - the frequency of occurrence of homozygotes for the dominant AA; 2 pq- frequency of occurrence of Aa heterozygotes; q 2 - the frequency of occurrence of homozygotes for the recessive aa.
The ideal population is a sufficiently large, panmictic (panmixia - free crossing) population in which there is no mutation process, natural selection and other factors that disturb the balance of genes. It is clear that ideal populations do not exist in nature; in real populations, the Hardy-Weinberg law is used with amendments.
The Hardy-Weinberg law, in particular, is used to roughly count the carriers of recessive genes for hereditary diseases. For example, phenylketonuria is known to occur at a rate of 1:10,000 in a given population. Phenylketonuria is inherited in an autosomal recessive manner, therefore, patients with phenylketonuria have the aa genotype, that is q 2 = 0.0001. From here: q = 0,01; p= 1 - 0.01 = 0.99. Carriers of the recessive gene have the Aa genotype, that is, they are heterozygotes. The frequency of occurrence of heterozygotes (2 pq) is 2 0.99 0.01 ≈ 0.02. Conclusion: in this population, about 2% of the population are carriers of the phenylketonuria gene. At the same time, you can calculate the frequency of occurrence of homozygotes for the dominant (AA): p 2 = 0.992, just under 98%.
A change in the balance of genotypes and alleles in a panmictic population occurs under the influence of constantly acting factors, which include: the mutation process, population waves, isolation, natural selection, gene drift, emigration, immigration, inbreeding. It is thanks to these phenomena that an elementary evolutionary phenomenon arises - a change in the genetic composition of a population, which is the initial stage in the process of speciation.
Human genetics is one of the most intensively developing branches of science. It is the theoretical basis of medicine, reveals the biological basis of hereditary diseases. Knowing the genetic nature of diseases allows you to make an accurate diagnosis in time and carry out the necessary treatment.
Go to lectures №21"Variability"
GENEALOGICAL METHOD(Greek genealogia pedigree) - compilation and analysis of pedigrees in order to establish patterns of hereditary transmission of normal and pathological traits.
The essence of G. m. is to clarify family ties and to trace a sign or disease among all relatives.
G. m, along with cytogenetic, twin, population-statistical methods and the method of modeling hereditary diseases, is one of the main methods for studying human heredity. In medical genetics (see) the method is more often called kliniko-genealogical as observe patol, signs by means of a wedge, inspections. A pedigree is compiled according to one or more characteristics of interest to a specialist.
G. m. is based on the patterns of hereditary transmission of traits established by G. Mendel (see Mendel's laws) and chromosome theory heredity (see). G. of m is in many respects equivalent to a hybridological method of the general genetics (see), but differs that at it instead of carrying out crosses from population select certain marriages and watch transfer of the interesting sign in generations. The genealogical method allows you to make probabilistic predictions about the occurrence of a particular trait or disease in a family. G. m. refers to the most universal methods in human genetics (see). It is used to establish the hereditary nature of the trait, determine the type of inheritance (see) and gene penetrance (see), study the mutation process, gene interaction (see). linkage of genes (see. Recombination analysis), mapping of chromosomes (see. Chromosome map).
The compilation of a pedigree for the analysis of inheritance in humans was proposed at the end of the 19th century. English scientist-anthropologist F. Galton. However empirical supervision over family trees in which inheritance patol, signs was noted, is known for a long time. For example, the Talmud reflected the dependence on the sex of inheritance of hemophilia. In the middle of the 18th century the inheritance of the dominant trait of polydactyly is described and an analysis of the splitting of this trait in the offspring is given. At the beginning of the 19th century Adams (J. Adams) on the basis of an empirical analysis of pedigrees described the dominant and recessive types of inheritance. At the same time, an analysis of the inheritance of hemophilia and color blindness was given. These and some other facts can be considered as prerequisites for the formation of the genealogical method. With the development of genetics as a science, genomics is being improved along the line of compiling pedigrees, and especially in relation to methods of statistical analysis of data. G. m. in the Soviet Union began to be widely used in the early 30s. 20th century S. N. Davidenkov, T. I. Yudin, Yu. A. Filipchenko, N. K. Koltsov and others.
In G. m., two stages can be conditionally distinguished - the compilation of pedigrees and genealogical analysis, i.e., analysis of pedigrees according to the principles of genetic analysis (see)
To compile the pedigree of the proband (the person with whom the examination begins), information is needed on the largest possible number of relatives - carriers of a hereditary trait or disease on the maternal and paternal lines. An essential condition for elucidating the features of inheritance is also a sufficient number of families in which the trait under study can be traced. The concept of "family" includes parents with children. Depending on the purpose, the pedigree can be complete (inclusion in the study of all families of relatives of the proband) or limited (inclusion in the study of only families with sick children). Sources for compiling a pedigree are usually direct examination, medical histories (or extracts from them), and the results of a survey of family members. Information about relatives should be clarified by cross-questioning.
The main element of the pedigree - the genealogical unit - is the individual.
When compiling pedigrees, generally accepted conventions(Fig. 1). Males are indicated by a square, females by a circle. In Great Britain, the symbol of Mars ♂ is used to designate males, and the symbol of Venus ♀ is used for females.
If there are several diseases in the family under study, the first letters of the names of these diseases are used.
Some authors recommend marking the age of each member of the pedigree at the appropriate places on the horizontal line, putting a cross before the age of the dead, and marking the personally examined family members with an exclamation point, which makes it possible to distinguish them from persons whose information was obtained from the answers of the proband or his relatives.
A graphic representation of a pedigree (genealogical table) is compiled in such a way that persons belonging to the same generation are located along one horizontal line. Usually drawing up a genealogy begins with a proband (see). If there are several children in the family, children are depicted from left to right, starting with the eldest. Sisters and brothers of one parental couple, considered together, are called sibs (see). Each previous generation is located above the proband line, and the next generation is below the proband line. For the convenience of compiling a pedigree, you can first draw pedigrees related to the mother of the proband ( maternal line), after which the paternal line is depicted or vice versa. Generations are indicated by Roman numerals, persons belonging to the same generation - by Arabic numerals. It is recommended to attach a textual description of its individual members to the pedigree - a legend.
The first stage of genealogical analysis (pedigree analysis) is the establishment of the hereditary nature of the trait. In each pedigree, the features of the inheritance of a particular trait should also be traced. When analyzing a trait, it is necessary to take into account its possible modifications as a result of the interaction of the gene that controls it and the environment. Thus, some diseases can manifest themselves only under certain environmental conditions; in other conditions carriers patol, a sign can be considered as healthy. A trait may depend on several genes. Outwardly similar traits are not always genetically identical. So, for example, muscle atrophy can be the main manifestation of myopathies (see) and develop as a result of alimentary dystrophy (see); subluxation of the lens in some cases is one of the main signs of Marfan's syndrome (see Marfan's syndrome), but it can be of traumatic origin. Signs that are identical at one level, for example, physiological, may be different at another, for example, biochemical. It is also important to establish whether two traits that coincide with each other are the result of the action of one gene or are due to the action of several genes. After the complete identity of the traits has been established, the study of ancestors and offspring using the selected markers makes it possible to establish, with a certain degree of certainty, the distribution of the corresponding genes among family members. At detection of repeated repetition patol, a sign or an illness in a family tree the careful genetic analysis for differentiation of hereditary pathology from phenotypically similar disturbances of other etiology is necessary. For example, microcephaly in combination with mental retardation may result from a rare recessive mutation; at the same time, some drugs taken by the mother during pregnancy, X-ray exposure of the fetus can cause similar defects. Rubella, suffered by a woman in the first three months of pregnancy, causes a variety of changes in the fetus (deafness, heart defects, eye damage), resembling signs of known hereditary diseases. Sometimes (mild rubella) the mother does not know about the disease she has suffered. In this case it is necessary to carry out serol, inspection of mother and the child to find out, than patol, signs at the child are caused: influence of an infection or influence of a mutant gene (see Mutation).
After establishing the hereditary nature of the analyzed trait*, they proceed to establish the type of inheritance. To address this issue, various methods of statistical processing of pedigree data are used.
The choice of method for processing genealogical data is largely determined by the method of collecting material.
With full registration of families, the direct a priori method of Bernstein or the simple method of siblings - the Weinberg method (see Population genetics) is more often used. With the direct a priori method, the expected number of sick children in a family with a certain number of offspring is calculated based on the dominant or recessive type of inheritance, and the existing distribution of sick children in families is compared with the theoretically expected one. At simple method of sibs, the ratio of sick sibs of the proband to the number of all sibs in the family is determined, after which a statistical comparison of the obtained ratio with the expected one is carried out, based on the dominant or recessive type of inheritance.
It should be borne in mind that a simple ratio of the number of sick children to healthy ones will not give a correct idea of the type of inheritance due to the fact that the analyzed material does not include carrier families in which normal children were born. The reason for this is often the fact that the registration comes from the patient. Therefore, the calculation of the ratio of sick and healthy children must be adjusted for the proportion of unexamined families. In case of incomplete single registration of the material, the Weinberg correction (W. Weinberg) is used. The essence of the amendment is that one sick child is excluded from each family and the proportion of remaining sick children to all remaining children in the family is determined.
Statistical analysis makes it possible to establish the relationship between the obtained data and the theoretically expected proportions of the mutant gene splitting, as well as to what extent the empirically found ratio corresponds to the Mendelian laws of splitting, to reveal the proportion of genotypes and other genetic patterns.
In a wedge, G.'s practice of m promotes clarification of the main laws of hereditary transmission patol, signs and diseases, establishment of types of their inheritance.
With an autosomal dominant type of inheritance (Fig. 2), the transmission of a hereditary disease or trait can be traced from generation to generation (vertical inheritance). Usually one of the parents of the proband is sick (rarely both) or he has erased signs of the disease; both sexes are affected with equal frequency. The probability of the appearance of a sick child in the family with full penetrance of the mutant gene (see Gene Penetrance) is 50%. In the presence of a mutant gene in both parents in children with a probability of 25%, the mutant gene is in the homozygous state. This leads to a particularly pronounced manifestation of the symptom. For example, with multi-fingering, both parents can give birth to children with very severe defects in the skeletal system.
It should be taken into account that the action of a gene largely depends on the modifying influence of other genes and environmental factors. Since the penetrance of the gene can vary over a wide range, the frequency of detection patol changes in a certain dependence, signs in the offspring. When checking genetic data regarding the inheritance of a dominant gene in the analysis of the pedigree, it is necessary to make an adjustment for the frequency of the trait in the population.
According to the autosomal dominant type, diseases such as Alport's syndrome (see), arachnodactyly (see), marble disease (see), osteogenesis imperfecta (see), Pelger's anomaly (see), Pernicious anemia (see) are inherited. , tuberous sclerosis (see), favism (see), Charcot - Marie amyotrophy (see. Muscular atrophy), etc.
With an autosomal recessive type of inheritance (Fig. 3), the effect of the mutant gene is detected only in the homozygous state (in the heterozygous state, the normal allele dominates), both sexes are equally affected, 25% of the children in the family are sick, 50% of the children are phenotypically healthy, but are heterozygous carriers of the mutant gene (like their parents), 25% do not have the mutant gene. The disease is often observed in siblings, while their parents and close relatives remain clinically healthy - the spread of a hereditary disease horizontally. The probability of having a sick child in two heterozygous parents is 25%; with a limited number of children in the family, for example, two, the probability of having two sick children is 6.25% (i.e. 0.25 X 0.25 X 100%). The probability of the birth of sick children increases significantly in the case of consanguinity of the parents, since this increases the possibility of combining two mutant genes in one zygote. This probability (with a penetrance equal to 100%) is determined by the formula q 2 + Fqp, where q is the frequency of the recessive allele in the population, p is the frequency of the normal allele, F is a coefficient equal to 1/4 (brother and sister, father and daughter), 1/8 (uncle and niece), 1/16 (cousin and sister), 1/64 (second cousin and sister). For example, if the parents are cousins, the risk of having an affected child with phenylketonuria is 1:1600, while in a marriage of unrelated persons it is 1:10,000. In the marriage of homozygous and heterozygous carriers (aa X aA), the number of patients children in the family increases to 50%, and half of the children will be heterozygous carriers of the mutant gene, which resembles an autosomal dominant type of inheritance (pseudodominance). The marriage of homozygous carriers of the mutant gene (aa x aa) leads to the birth of children who are also homozygous carriers of this gene and have a wedge, signs of the disease. In some cases, children may be phenotypically healthy, which may indicate that the studied trait or disease is controlled by different genes (genocopy).
According to the autosomal recessive type, the following are inherited: alkaptonuria (see), albinism (see), amaurotic idiocy (see), galactosemia (see), hepato-cerebral dystrophy (see), lactic acidosis (see), cystic fibrosis (see), Niemann-Pick disease (see), progeria (see), Refsum syndrome (see), etc.
With a recessive sex-linked type of inheritance, the mutant gene is localized on the X chromosome or Y chromosome. The inheritance of genes localized on the X- and Y-chromosomes occurs according to the patterns established for the sex chromosomes. The features of inheritance vary depending on the localization of the gene in the homologous or non-homologous segment of the X- and Y-chromosomes. So, the hollandic gene (a gene absolutely linked to the Y-chromosome), which causes webbed fingers, hairy auricles and some other features, is inherited through the paternal line and manifests its effect only in males. The transmission of a hereditary defect from a father to all his sons occurs with complete penetrance of the mutant gene.
When the mutant gene is localized on the X chromosome, women carrying the mutant gene remain phenotypically healthy because the normal allele of the second X chromosome opposes the mutant gene. The effect of a mutant gene located on the X chromosome is manifested only in males, with the exception of extremely rare cases when both X chromosomes carry the mutant gene. In a family, half of the boys may be sick, and half of the girls may be carriers of the mutant gene (Fig. 4). Affected men pass the gene on to their daughters and not to their sons. According to the recessive sex-linked type, the following are transmitted: agammaglobulinemia (see), Wiskott-Aldrich syndrome (see), hemophilia (see), color blindness (see Color vision), Lowe syndrome (see), Fabry disease (see) and etc.
When analyzing pedigrees, it is necessary to take into account the possibility of a polygenic type of inheritance. At the same time, the number of genes that control a certain trait can be quite significant. Polygenic is the hereditary basis of such traits as growth, mental development, temperament. Their manifestation is also significantly affected by the influence of the environment.
G. m allows you to clarify the nature of hereditary transmission, which is important for the timely diagnosis of the disease and therapy in the early stages of the disease, solving a number of issues in the medical genetic consultation (see). Thus, the compilation of a detailed pedigree is necessary, in particular, to determine the prognosis of offspring. Indications for the use of G. m in such cases - the presence in families of persons with a hereditary disease or indications of aggravated heredity. G. m. determines the indications for the choice of an additional (paraclinical) method of examination, which is of great importance for identifying the heterozygous carriage of the mutant gene.
The accuracy of G. m is limited by a small number of children in the family. Errors in using the method may also be due to incorrect diagnosis of the disease (sign); incorrect determination of paternity due to extramarital affairs. Incorrect diagnosis is usually associated with insufficient differentiation of pheno- and genocopies, with insufficient information obtained due to the extensiveness of the pedigree, and insufficient knowledge of the respondents about certain analyzed traits in relatives. Often surveyed do not know the relatives or try to hide existence of hereditary illness, patol, a sign, to shift them to other line. G.'s inaccuracy of m can also occur due to the registration of families with a different number of patients, the absence of sick children in heterozygous carriers. Incomplete penetrance of a dominant gene or incomplete dominance can mimic recessive inheritance. G. of the m in some cases does not give the reliable data allowing to distinguish the dominance limited by a floor, from the recessive inheritance linked to a floor, as, for example, at the sick father the clinically healthy daughter has a sick son. In addition, it is difficult to distinguish a newly arisen mutation from a previously existing one in the pedigree. Penetrance and expressivity of the mutant gene vary in heterozygous carriers with autosomal dominant inheritance. In these cases, it is important to take into account even the erased and atypical signs of the disease and paraclinical research, which helps to correctly establish the type of inheritance.
Thus, the analysis of pedigrees precedes the clinical and laboratory examination of patients and their relatives. G. m makes it possible to determine the type of inheritance patol, trait or disease and thereby often clarify its form, since transmission is characteristic of each hereditary disease mainly by a certain type. The features of transmission of a hereditary disease established by means of G. of m allow to approach the analysis of early wedges correctly, the symptoms revealed at some members of the studied family have differential and diagnostic value. So, in the initial stages, it is difficult to diagnose the main forms of myopathy: pseudohypertrophic, juvenile, and shoulder-scapular-facial. The study of genealogical data can help to correctly assess the wedge, the symptoms of the disease, determine its form, since the pseudo-hypertrophic form is characterized by a sex-linked type of inheritance, for the juvenile form it is autosomal recessive, and for the shoulder-blade-facial it is autosomal dominant. From these positions, G.'s data of m are often important for the timely diagnosis of hereditary diseases - before the development of pronounced stages of the disease. G. m can give an indication of the cause of the disease in some clinically difficult cases. So, a child with signs of damage to the nervous system, reminiscent of phenylketonuria (see). While biochem. there is no defect, it can be born from the marriage of a woman with phenylketonuria and previously treated, with a healthy man (toxic effect of phenylalanine on the fetal brain). G. m. makes it possible to determine the circle of people who need detailed studies to identify the heterozygous carriage of the mutant gene, first of all, close relatives of the proband, people with a burdened history. A wedge, inspection of the last has to be complex, with special attention to identification of the microsymptoms identical to those at a proband. Analysis of genealogical data is the basis for choosing the necessary method of paraclinical research: hematol, examination for blood diseases, biochemical, methods for metabolic disorders, electromyography for neuromuscular diseases, electroencephalography for epilepsy, etc. G. m. also allows you to identify the role heredity in the development of a number of common non-hereditary diseases: cardiovascular, rheumatism, neuropsychiatric and some others.
G. m. helps to trace the features of inheritance over a number of generations, to note the influence of external factors, blood marriages on the manifestation of the mutant gene and the degree of severity of its properties. In recent years, computers have been increasingly used to study the pedigree. The practical value of G. m. increases with an increase in the accuracy of drawing up pedigrees; this is facilitated by a more complete registration of genealogical data and the identification of teterozygous carriers of the mutant gene through a comprehensive examination.
Bibliography: Badalyan L. O., Tabolin V. A. and Veltishchev Yu. E. Hereditary diseases in children, M., 1971; Davidenkov S. N. Hereditary diseases of the nervous system, M., 1932; he, Clinical Lectures on Nervous Diseases, c. 4, M 1961 Konyukhov BV Biological modeling of human hereditary diseases, M., 1969; Makkyosak V. Human genetics, trans. from English, M., 1967; he, Hereditary signs of man, trans. from English, M., 1976, bibliography; Neil J. V. and Shell W. J. Human heredity, trans. from English, M., 1958; Problems of medical genetics, ed. V. P. Efroimson et al., M., 1970; Stern K. Fundamentals of human genetics, trans. from English, M., 1965; Efroimson V. P. Introduction to medical genetics, M., 1968; Roberts G. A. An introduction to medical genetics, L., 1963.