Heritability of multifactorial disorders, X-linked heredity seminar No 427 Heredity

X-linked heredity Key words: sex-linked traits, completely and incompletely sex- linked traits, gonosomes (heterochromosomes), hemizygote, gonosomal dominant heredity (XD), gonosomal recessive heredity (XR), holandric heredity, testes determining factor (SRY), sex influenced and sex limited traits

X-linked heredity 1. A woman is a carrier of hemophilia (XR disorder). What is her chance of having 6 sons - three healthy and three affected with hemophilia? 2. A woman is a carrier of hemophilia (XR disorder). What is her chance of having 6 children - three healthy and three affected with hemophilia? 3. Explain situation in following three pedigrees. A man (III/1) has DMD (Duchene muscular dystrophy, XR disorder). What is the difference among this pedigrees? What is the risk that women are carriers of DMD?

a) b) c)

4. A couple is healthy. Wife´s father suffered from hemophilia A. Husband´s parents are healthy, but his maternal grandfather suffered from hemophilia A. What is their risk of having an affected son, an affected child? 5.A woman has maternal grandfather affected by hemophilia A. What is her risk of having an affected child, an affected son? 6.What are the situations, in which woman suffer from hemophilia? 7. What woman is obligatory carrier of hemophilia?

9. Defective development of dental enamel is gonozomal dominant (GD) disorder. a) A healthy woman married an affected man. What is their chance of having an affected daughter, an affected son? b) An affected woman married healthy man. What is their chance of having all four children healthy ? 10. A man suffers from hemophilia and color blindness. Will all his daughters carriers of both alleles? What is the probability that his daughter´s sons will be affected by this disorders?

11. A man with hemophilia marries normal female from healthy family. What is the probability they will have affected offspring? What is the probability they will have an offspring - carriers of hemophilia? 13. Premature baldness in man is dominant trait. In heterozygous genotype this trait is expressed only in presence of male hormones, in female heterozygotes this trait is not manifested. What are genotypes and phenotypes of male and female offsprings of these couples? a) mother bb x father BB b) mother Bb x father Bb c) mother BB x father bb d) mother bb x father bb.

Polygenic heredity Key words polygenic, multifactorial heredity, quantitative traits, theory of threshold, hereditary predisposition, empiric risks, preconceptional care, Edwards formula, twins study, concordant and discordant traits, heritability

Calculation of heritability from twin studies Heritability H = degree of genetic determination of trait, disorder Twin studies: MONOZYGOTIC twins - genetically identic DIZYGOTIC twins - genetically as siblings Concordant traits - both members of twin pair exhibit a certain trait Discordant traits - only one member of twin pair exhibits a trait CMZ - CDZ H = 100 – CDZ

2) What is value of heritability for a) schizophrenia, if concordance of monozygotic twins is 75%, concordance of dizygotic twins 15%. b) hypertension, if concordance of monozygotic twins is 35%, and dizygotic 2,7% 3) Calculate the risk of cleft palate for the 1st degree relatives, if frequency of this disorder in population is 0, ) Two healthy parents have a daughter with spinal cleft Frequency of disorder in population is 0,0009. What is the risk of abnormality for the next pregnancy? What will be the risk for a child of affected daughter? 5) One member of monozygotic twin pair exhibits AD disorder, second member not. Explain possible causes.

Thompson and Thompson: Clinical genetics, chapter 8 : Complex inheritance, pg , 7th edition