Chapter XII - Medical Biology - Course Content Genetics 2023-2024 PDF

Exercise 12 Topic: Multifactorial traits. Quantitative inheritance in humans. Glossary: Cumulative genes (polygenes) - genes that determined quantitative traits. Empirical risk - the degree of risk based on data from direct observation and the study of a large number of families. Fingerprints (derma...

Exercise 12 Topic: Multifactorial traits. Quantitative inheritance in humans. Glossary: Cumulative genes (polygenes) - genes that determined quantitative traits. Empirical risk - the degree of risk based on data from direct observation and the study of a large number of families. Fingerprints (dermatoglyphs) - configurations of ridged skin on the hands and feet; the term also applies to the science embracing their study (i.e. the scientific, clinical and genetic study of finger and palm prints). Heritability - one of the basic properties of each quantitative trait, determiningwhich part of the trait variability depends on the influence of genes, and which on the environment; is a genetic component of the total phenotypic variation of a given trait. Intelligence quotient (IQ)–the measure of intelligence (mental abilities); the numerical value of the psychometric test. Monogeneous traits (monogenic) - traits conditioned by one pair of allelic genes. Multifactorial inheritance - a type of inheritance influenced by both the genetic factor (many non-allelic genes) and the environment. Multifactorial qualitative traits - traits conditioned by genetic-epigenetic factors and the environment, the variability of these traits is not continuous (changes by leaps and bounds), their occurrence is determined by exceeding the threshold of genetic sensitivity. Multifactorial quantitative traits - traits conditioned by genetic-epigenetic factors and environments that change continuously (the normal distribution curve, Quetelet);they can be measured and their intensity can be expressed numerically. Multifactorialtraits - traits conditioned by genetic-epigenetic factors (polygenic variability, including polymorphic variability) and the influence of environmental factors. These traits show population and intra-familial variability. We divide them into quantitative and qualitative multifactorial features. Multigenic (polygenic) inheritance - type of inheritance, in which the features are conditioned by the interaction of a number of non-allelic genes, the effects of which sum up (cumulative, additive effect). Polygenic traits – traits conditioned by the interaction of two or more pairs of non-allelic genes. Transgression - exceeding the range of the intensity of the characteristics occurring in the parental generation (e.g. children taller or lower than parents). Multifactorialtraits Most features in living organisms, both plants and animals, are so-called multifactorial features that occur in each individual, but with varying intensity. Multifactorial features are determined by the interaction of multiple pairs of genes at different loci (each of which has a small but additive effect) and environmental factors. If only genetic factors are taken into account, inheritance is defined as multi-genetic (polygenic). Each pair of genes determining a multifactorial feature inherited according to the Mendel's law. The definition of a multifactorial feature includes both its family nature and dependence on environmental influences. An environmental component is the broadly understood impact of the environment, i.e. factors such as diet, temperature, climate, environmental pollution, etc. It is the determination of predispositions (tendencies). Multifactorial quantitative traits This group includes numerous normal and some pathological phenotypic features. The degree of development of the quantitative trait depends on the number of genes (poligenes) dominant (active) with additive effects and recessive (neutral) genes. Examples of multifactorial quantitative features: a) normal: height (depending on 400 genes), body weight, intelligence, pigmentation of skin, eyes and hair, total number of fingerprints, number of erythrocytes, blood pressure, serum cholesterol, anthropometric measurements; b) pathological: obesity, hypertension, susceptibility to infection. The frequency of multifactorial quantitative traits in the population is normally distributed. The distribution of the intensity of multifactorial quantitative traits in the population generally shows continuous variation, which means that it can be different and lie between extreme values. In each population, there are individuals with the extreme (minimum and maximum) intensity of a given trait, but most individuals exhibit its intermediate (average) intensity. For example, regarding the height, there is a wide range of the intensity of the feature: from short low to very tall. Figure 1. The Gaussian curve showing the distribution of the multifactorial quantitative traits in the population. The distribution of the trait intensity depends on the number of polymeric genes conditioning the given trait and if this number increases, then the binomial distribution of the phenotype frequency approaches the Gaussian curve (Figure 1). This curve shows the distribution of the intensity of the quantitative trait, resulting from the genotype and the impact of environmental factors. The frequencies of identical phenotypes for the number of dominant alleles are the values of the numerical coefficients for consecutive words of the developed Newton binomial theorem : (a + b) n, where "a" and "b" are the frequencies of genes in the population, and "n" is the number of genes. The numerical coefficients of the developed Newton binomial are most easily calculated using the Pascal triangle (provides Newton's binomial coefficients depending on the n value): In genetics, the Pascal triangle coefficients are used only for the second generation (F2); they mean the number of individuals in the following classes in attribute multifactorial quantitative traits; i.e. a gradually increasing number of alleles predisposing to a greater intensity of a given trait depending on the total number of alleles of the trait (n). With increasing number non-allelic pairs of genes for a characteristic frequency distribution of phenotypes approaches the normal distribution. The number of genotypes is given by the formula: 3 a, where "a" is the number of allele pairs. The number of phenotypes is smaller than the number of genotypes. The number of different phenotypes equals the number of single dominant genes (n) plus 1 (n + 1). Extensive phenotypes of the multifactorial quantitative traits occur at a frequency (1/2) n, where "n" is the number of single non-allelic genes. If, for example, a trait depends on three pairs of polymeric genes, then we consider six alleles, i.e. we use a six series, in which the distribution is as follows: 1 6 15 20 15 6 1 so the number of individuals with an intensity of the traits: the maximum (6 alleles predisposing to high growth) - 1; greater than average, but less than the maximum (5 alleles) - 6; greater than average, but smaller than the maximum (4 alleles) - 15; medium (3 alleles) - 20; greater than the minimum, but less than average (2 alleles) - 15; greater than the minimum, but less than average (1 allele) - 6; minimum (0 alleles predisposing to high growth) - 1. You can also write gametes created by each individual and fill in the Punnet’s table: F2: In the table, we only enter the sum of alleles that increase the intensity of the trait - the phenotypes depend on the number of alleles predisposing to greater height - that is, they determine the intensity class of the trait: The number of dominant genes conditioning a quantitative trait: 6 5 4 3 2 1 0 The number of individuals in the feature intensity class: 1:6:15:20:15:6:1 In the second generation, the combination of eight different gametes from each parent gives us the possibility of 64 genotypes (descendants in the F2 generation). Quantitative traits which in healthy people have continuous variability may show significant variations due to the influence of other genetic or environmental factors, e.g. achondroplasia may significantly reduce the growth of a child that would normally achieve an average iheight. A high-parent child is likely to be higher than a low-parent child, but poor nutrition can limit the growth of each of these children. For example, hypertension, apart from genetic factors, may be affected by lipid levels, obesity and stress. Genetic predisposition to the occurrence of multifactorial traits is usually inherited from both parents. The study of the distribution of beads in the Galton apparatus is a distribution model of the intensity of quantitative traits with continuous variation in the population. The experiment is aimed at determining the histogram of the binomial distribution and comparing it with a histogram reflecting the Gaussian curve (Pascal triangle coefficient). The Galton apparatus is an array(at an angle of 45°) with metal nails (symbolizing environmental factors) arranged at regular intervals in horizontal rows. Each row is moved from the previous one by half the distance between two nails. There is a triangular chamber above them in which balls are placed (representing individuals of a hypothetical population), while under the nails, there are 11 chambers (representing intensity classes of the quantitative feature). After colliding with the nails, the balls fall into the chambers placed at the bottom of the apparatus. The balls falling from the top are deflected off the nails on different sides, the probability that the ball will be directed to the right is the same as pointing it to the left and is 0.5. As a result, the final distribution of beads in the Galton Apparatus is completely random and illustrates the distribution of the intensity of the quantitative trait in the population under natural conditions affected by small random deviations. The highest percentage of individuals shows an intermediate intensity of traits, while individuals with extreme intensity of features present the lowest percentage. Children tend to resemble their parents in terms of physiological characteristics, determined by genetic factors (parents with above-average height often have children higher than average). In the case of physiological quantitative traits, children tend to achieve an average of the values of their parents' traits. The children of parents who have extreme values of a multifactorial traits tend to achieve more average values - this is referred to as so-called regression to the average. In the case of parents with less than average traits, the same phenomenon is observed, and the tendency to equalize traits to the average is all the more evident, the greater the deviation of the parents' traits from the population average. In the case of inheritance of multifactorial features, it is also possible to observe the exceeding of the scope of the characteristics determined by the parental generation, the so-called transgression: positive or negative. Examples of transgression in the human population may be: Mulatto children with a skin tone lighter or darker than their parents, children taller or lower than parents, more or less intelligent or more or less immune to infectious diseases but also children with a multifactorial disease that did not occur in their parents. Multifactorial quantitative traits Intelligence (Raymond B. Cattell): 1. liquid: - depends on the brain structures and functions which determine concentration, quick association, and the rate of mental work 99/5000 - reveals itself mainly in solving wordless tests (recognition of relations between elements), - the highest level is reachedby 18-21-year-olds, it decreases as a consequence of aging of the brain; 2. crystallised: - develops on the basis of fluid intelligence as a result of learning and acquiring experience (understanding tasks, detecting analogies, defining the meaning of words), - it is culturally defined, and develops to old age. Francis Galton was a pioneer of scientific research on intelligence. Remaining under the influence of Charles Darwin, he claimed (1883) that intelligence is the basic ability of the mind, decisive for the individual's success in the "struggle for existence". Definitions of intelligence - examples: - Jean Piaget – intelligence is a developed form of biological adaptation (the concept of intellectual development). Mental development concerns better adaptation, accompanied by an increase in the complexity and effectiveness of cognitive structures. - Robert Sternberg – intelligence is an individual phenomenon belonging to the inner world of the individual as a phenomenon determined by the external world and reflected in the experiences of the individual (triarchic theory of intelligence). Intelligence quotient IQ - the measure of intelligence (mental abilities), indicator evaluating the degree of mental development:  children - the quotient of mental age to the age of life, multiplied by 100,  adults - the so-called deviant IQ, developed by D. Wechsler. Deviant intelligence is marked on a scale in which the average result for a given population is assigned a conventional value of 100, and the standard deviation from the average - a conventional value of 15. The index calculated in such a way, mathematically allows to assess the intellectual level of the individual against the background of the entire population. Wechsler Intelligence Scale - 11 tests:  6 verbal: messages, understanding, arithmetic, repeating numbers, similarities, dictionary,  5 non-verbal: sorting images, missing images, jigsaws, blocks, symbols of numbers. Verbal scale - verbal and conceptual functions: 1. News - the resource of messages acquired during the education process and in the course of life experiences; the scope of knowledge and the ability to organize and store it; it is required to understand the facts and remember them. 2. Similarities - the ability to create and understand concepts, and thus to organize all the messages received; the ability to classify based on basic thought processes, ordering, abstracting, comparing, and generalizing. 3. Arithmetic - measures the ability to reason and perform accounting operations, mental activity and the ability to concentrate. 4. Dictionary - illustrates the state of knowledge, measures the scope of concepts and experiences that the individual has gained during his/her life. 5. Understanding - measures the level of understanding of the situation and judging, measures the ability to use the possessed messages according to the situation. 6. Repeating numbers - measures the ability to focus attention and direct memory. Non-verbal (executive) scale - specific and pictorial functions: 1.Replenishing pictures - require the ability to concentrate, and extract inconsistencies and discrepancies in the perceptual material. 2. Organizing pictures - the ability to logically organize the material; the ability to anticipate events and plan effective directions of action. 3. Patterns from blocks - the ability to analyse and synthesise visually perceived material; analysing and differentiating parts and determining the relationship between these parts in such a way as to form a whole. 4.Puzzle - the ability to create a whole, by detecting internal relationships between elements. 5. Coding – therate of visual and motor learning, effectiveness of using psychic energy in performing homogeneous tasks. It is estimated that 95% of the population exhibits IQ 70-130, 68% have an IQ between 85-115, 2% have an IQ below 70 and above 130, while 0.1% have an IQ below 55 and above 145. The only qualifying condition for membership in Mensa (an international association of people with a high IQ, named after the Latin name mensa- table, referring to the idea of a round table, where there are no more important and less important places) is to pass the Mensa test of intelligence with the result that places the test taker in 2% of the population with the highest IQ. Group tests are organized from time to time in major cities, there is also the possibility of individual examinations at Mensa psychologists. The condition of joining the test is the documented age over 15 years. Tasks for the test are prepared by the Americans, tests are secret. Mensa tests do not contain typical math problems. Questions change on average every 5 years. Examinees have 20 minutes to solve 45 tasks. The result of the test is kept secret - it is nowhere to be published. Statistically, approximately 30% of the persons pass the test. Some famous members of Mensa: Art: director: Geena Davis: actor: Steve Martin; writer, computer scientist and drummer: Nelson DeMille: writer: Arthur C. Clarke; science-fiction writer: Derek Keith Barbosa Science: inventor, considered the creator of a mobile phone: Martin Cooper; lawyer, biochemist: Lancelot Ware; author of science-fiction and biochemist, former vice president of Mensa International: Isaac Asimov Howard Gardner, American psychologist and specialist in cognitive psychology, divided our intelligence into visual-spatial, verbal, musical, interpersonal, intrapersonal, bodily-kinesthetic, logical-mathematical, natural, existential and moral-ethical (theory of multiple intelligence). The overall picture of IQ is so complex that it cannot be measured by using one test. The tests, in which there are mathematical puzzles, check the condition of our logical-mathematical intelligence. The IQ tests do not give a reliable result because you can train yourself in solving logic tasks. This type of task uses some repetitive tricks, the number of which is limited. If you solve all tasks and subsequent tasks, and then match individual tricks to each task, you can get a high IQ, even if youare a person with average mental abilities. Fingerprints - dermatoglyphs: The distinctive arrangement of epidermal strips, between which there are grooves, especially on the tips of the fingers, but also on the inner surface of the hands and toes. They occur in humans and other primates. The slats fulfil sensory functions in the body (tactile stimuli) and mechanical functions (they support the grip of the hands and feet to the ground). This system can be equipped with 3 pairs of interacting genes (qualitative traits), located on different chromosomes. The line pattern is inherited as qualitative traits, whereas the number of skin slats is a quantitative trait. The fingerprint system, genetically determined, is modified by internal environment"system factors", hence differences arise in the papillary pattern between fingers of the left and right hand. Dermatoglyphs develop in a human in the 13th-19th week of foetal life (3-5 months of foetal life), their system is formed at the end of the 6th month of foetal life. During the development processes, the lines grow: increasing the length, height and width, without disturbing the proportion of slat construction. Flexural creases occur in places of refraction of the hands and feet. The main folded furrows also arise during foetal life - unchanging in lifetime. Three laws formulated by Francis Galton proclaim that the fingerprints are:  individual - like the genome, are different even in monozygotic twins,  immutable,  indestructible. Dactylogram is a mapping of the fingerprint layout. It is a unique and almost indestructible feature. The element of classification is the so-called delta = three-armed = three-pronged. Therearetwotypes of delta:  bifurcated (atypical) - arises from a bifurcation of the fingerprint line  typical - arises from two fingerprints next to each other.. There are three basic types of patterns:  arch - a rectangular without delta, the slats run from one side of the finger to the other, with a slight elevation in the middle,  loop – with one delta, slats start and finish their course on the same side in relation to the open part of the pattern (depending on the direction of the loop may be ulnar or radial),  whorl - a closed pattern, at least one of the lines performs rotation around its axis, two columns - two RC indices (Ridge Count), when calculating TRC (total ridge count) we take into account the slats on the side of the pattern whose numerical value is larger. Detailed classification of skin slat designs on the hand fingers: arch, tent arch, loop, rocket loop, shell loop, whirl, circular dicentric whirl, elliptical dicentric whirl, double loop, gamma loop, complex pattern, atypical whirl. Dactylogram analysis - evaluation of RC and TRC indices Combining the bifurcation of the delta with the centre of the fingerprint pattern, we get the Galton line. The number of fingerprints crossing the Galton line (excluding the delta line) is the RC index (ridge count), and the sum of RC indices for 10 fingers is a TRC index (total ridge count). The frequency of different patterns varies depending on the gender: women have more often arched patterns and less frequently vortex patterns compared to men. TRC for women (46, XX) is ≈ 129, and for a man (46, XY): ≈ 146. In the analysed fingerprint systems, there are also very rare elements called - minutiae. Types of minutia of skin slats (according to Grzeszyk): beginning, ending, single bifurcation, double bifurcation, triple bifurcation, single connection, double connection, triple connection, hook, single eye, double eye, single bridge, twin bridge, point, segment, side contact, passing line, intersection, tripod, residual line, minutia type "M", "m". Changes in dermatoglyphic patterns similarly to skeletal anomalies, they are considered to be a sensitive indicator of disorders occurring in the foetal period. Characteristics of dermatoglyphic systems in diseases:  Turner’s syndrome - increased number of slats on the fingertips (increased TRC ≈ 165), usually the dominance of whirl patterns, higher position of the axial triangle (distal or indirect);  Down’s syndrome - more frequent occurrence of ulnar loops on the fingertips, (Down's syndrome:> 82%; 46, XX and 46, XY: about 65%), whirls occur less frequently (Down's syndrome: 13.4%, 46, XX and 46, XY: approx. 24%), distal arrangement of the axial triple radius in 86% (in healthy people proximal layout in 64% cases), in the area of the withers of the finger V, the system of skin slats is richer in patterns, the most common pattern is ulnar loops, fourfinger flexion furrow (so-called transverse furrow) in 50-70% of people, there is excessive laxity skin on the hands and feet, and thus an increased number of folded furrows, there are islet and islet-lap systems on the feet, the socalled dissociations (instead of typical skin slats their forms are very short: segments and islets arranged chaotically), rarely found in healthy people. A very rare feature is adermophilia, which is characterized by a lack of epidermal slats on the hands and soles of the feet. This results in the lack of fingerprints and is associated with a smaller number of sweat glands and, consequently, reduced sweating of the hands and feet. The total lack of slats causes difficulties in gripping or holding objects. There are mild hyperkeratosis of the hands and calluses on the soles. This is an inherited autosomal dominant trait, caused by a heterozygous mutation in the SMARCAD1 gene located on the 4q22 chromosome. Dermatoglyphs and flexural furrows can be observed already during the ultrasound examination of the foetus. It is possible to observe changes in the case of developmental disorders, e.g. the presence of a transverse furrow (Figure 2). Figure 2. Hand of a person without transverse furrow (A) and hand of a person with transverse furrow (B) (http://www.handresearch.com/news/the-real-hillary-clinton.htm). In Poland, in the population of healthy people, the transverse furrow occurs in 1% on both hands and in 4% on one hand; in about 40% of people with Down syndrome. In other populations, the incidence of transverse furrow is different (Table 1). Table 1. Frequency of transverse furrow in different populations (according to Sharma and Sharma, 2011) Lp. Population Frequency of transverse furrow on one hand [%] 1 Pygmies 34.7 2 Hindus 14.4 3 Gypsies 14.3 4 Chinese 13.0 5 Koreans 11.2 6 Japanese - Kyushu region 9.2 7 Arabs and Berbers 7.9 8 Jews 4.6 9 Ijaw - Nigeria 4.1 10 Japanese - eastern region 4.0 11 Germans 2.8 12 Iranians 2.5 13 Ajnowie - the island of Hokkaido 2.2 14 The Dutch 1.5 15 Eskimos 1.3 Multifactorial qualitative traits Multifactorial qualitative inheritance is a frequent cause of congenital defects or chronic diseases. The predisposition to a given disease / defect is inherited, and its manifestation depends on many gene loci shaping the tendency and on the type and strength of the environmental factor (trigger factor). Examples of qualitative multifactorial features: a) congenital malformations: cleft lip and / or palate, certain forms of congenital heart defects, neural tube defects (spina bifida, anencephaly), foot deformation, narrowing of the pylorus, congenital dislocation of the hip joint; b) adulthood illnesses: rheumatoid arthritis, multiple sclerosis, diabetes (type I and II), premature atherosclerosis, coronary heart disease, bronchial asthma, stroke, hyperthyroidism, epilepsy, schizophrenia, Alzheimer's disease, bipolar affective disorder, some cancers. Qualitative (discontinuous) traits in the population do not reflect the distribution consistent with the Gaussian curve.The threshold model (Figure 3) for the inheritance of qualitative multifactorial traits explains how multifactorial predisposition to a disease or malformation may cause it. Figure 3. The threshold model in qualitative multifactorial diseases with regard to gender differences (according to Jorde et al. 1995). According to this model, all individual, genetic and non-genetic predisposing factors determine the susceptibility of the individual to the disease. This vulnerability in the population is normally distributed, but the disease will occur, when a certain threshold of genetic predisposition (susceptibility threshold) is exceeded; the more this threshold is exceeded, the greater the severity of the defect / disease. People on the left side of the vulnerability schedule are slightly exposed to the disease (i.e. they have few alleles that tend to develop or are influenced by few environmental factors), and people closer to the right end of the distribution have more genes predisposing to the disease and are subject to more environmental factors, therefore they are more likely to develop the disease. The vulnerability threshold may have different values for sex. The occurrence of different susceptibility thresholds in women and men indicates that both sexes need different numbers of susceptibility genes for the development of the disease. In the case of discontinuous multifactorial features, the risk for family members burdened with the occurrence of the disease is higher than the population risk and clearly decreases for further relatives, approaching the population risk (Figure 4). Figure 4. The threshold model in multifactorial diseases for members of the family burdened with the occurrence of the disease (according to Passarge, 1995). In practice, a proband manifesting a discontinuous multifactorial trait is often the only sick person in the family. In contrast to single-gene diseases, pedigree analysis cannot provide evidence for multifactorial inheritance and it is necessary to carry out studies on the compatibility of twins and family correlations (to distinguish multifactorial features from single-genes or caused by non-genetic factors). Compatibility test of twins Twins are compatible if they exhibit the same discontinuous feature, and incompatible if only one of them has this feature. With regard to continuous features, feature is directly compared between twins.Since twins usually grow under the same family conditions, it may be difficult to distinguish the impact of environmental and genetic factors on the development of a given multifactorial feature. For this reason, the most important are tests for the compatibility of monozygotic twins (MZ), who have beenput up for adoption and separated in their infancy. Compatibility level of the occurrence of multifactorial traits in dizygotic twins (DZ) is much lower than in the MZ twins and usually similar to the risk of recurrence of disease in the remaining siblings. For each multifactorial feature, conformity between monozygotic twins the compliance of MZ twins exceeds that observed for twins, although the range of conformity among MZ twins varies from 6 to 100%. This range reflects the degree of inheritance of the disease: the greater the compatibility of the MZ twins, the greater the share of genetic factors in the occurrence of the trait and the greater heritability. Although studies of twins provide valuable information, they are burdened with some errors, for example, somatic mutations during mitotic divisions of embryonic cells that can affect only one of a pair of twins, or differences in the uterine environment. The problem resulting from the greater degree of environmental similarity in monozygotic twins can be at least partially eliminated by studying monozygotic twins brought up in different environments. Research on family correlations: If a trait is subject to multifactorial inheritance, relatives should demonstrate its presence according to their mutual genetic similarity. This study is an extension of the technique for testing the compatibility of twins, and the similarity of relatives in terms of a given feature is called their compatibility; the similarity is shown on a scale from 0 to 1, where 1 is identity. The closer the relationship between two relatives, the higher the compliance ratio for genetically determined traits. The incidence of discontinuous traits in the relatives of a sick person decreases with the decreasing proportion of common genes, however, for all relatives it remains higher than the frequency found in the general population. In summary, compatibility test of twins and family correlation tests can provide evidence of a multifactorial inheritance of a feature, whether it is continuous or discontinuous. Determining the relative impact of genetic and environmental factors on the multifactorial feature could help to better understand the aetiology of many diseases and to apply specific preventive measures as part of the public health strategy. Diseases in which the impact of hereditary factors is relatively small (e.g. lung cancer) can be most effectively prevented by changing the lifestyle (cessation of smoking). However, when the disease depends mainly on genetic factors (e.g. breast cancer), apart from lifestyle changes, it is also necessary to analyse the history of the disease in the family. Based on the phenotypic similarity between first-degree relatives, heritability is estimated which determines which part of the phenotypic variability of a multifactorial feature is conditioned by genetic factors, and which depends on the environment. The value of this indicator ranges from 0 to 1; 0 - means the total environmental impact, 1 exclusive influence of genetic factors. The values of inheritance are characteristic of the population in which they are determined. Mathematically, heritability is expressed by the formula: VG - variance depending on the genotype VS - variance depending on the environment VC - variance related to the measurement error VG + VS + VC = total phenotype variance. The risk of recurrence of the disease and patterns of its transmission: Unlike most monogenic diseases, the risk of recurrence of multifactorial diseases can vary significantly in different populations. Some multifactorial features are more common in people of one sex, for example, pyloric stenosis is 5 times more frequent in boys, a congenital dislocation of the hip joint - about seven times more frequent in girls. The risk of re-occurrence of the same disease in the family is the same for all relatives having the same part of common genes and drops sharply as the relationship to the sick person diminishes. Multifactorial diseases are much more frequent among children of relatives because they have more common genes predisposing to the development of the disease. The risk of disease recurrence is higher if more than one of close relatives is ill;it is higher for relatives of those probands, whose sex is less frequently affected by the disease, and is also higher if the expression of the disease is stronger (more severe form of the disease). Environmental factors have the highest impact on the occurrence of the disease in a person with genetic predisposition, which means that the identification of environmental factors predisposing to the onset of the disease should be the easiest in genetically predisposed individuals. Moreover, in such people, the control of environmental factors in order to prevent the disease may be the most effective. It should be remembered that it is possible that genetic heterogeneity may occur, which causes some cases of the disease to be inherited according to Mendel’s inheritance pattern, while others have non-genetic or multifactorial causes. References: 2. Campbell, J.B. Reece: Biology. Pearson, Benjamin Cummings, Seventh Edition 2005 3. Jorde L.B.; Carey J.C.; Bamshad M.J.; White R.L.: Medical Genetics, Third Edition 2006