Sex-linked Traits

1. Sex-linked Traits • Traits (genes) located on the sex chromosomes • Sex chromosomes are X and Y • XX genotype for females • XY genotype for males • Many sex-linked traits carried on X chromosome

2. fruit fly eye color XX chromosome - female Xy chromosome - male Sex-linked Traits Example: Eye color in fruit flies Sex Chromosomes

3. Xr Xr XR Y Sex-linked Trait Problem • Example: Eye color in fruit flies • (red-eyed male) x (white-eyed female)XRY x XrXr • Remember: the Y chromosome in males does not carry traits. • RR = red eyed • Rr = red eyed • rr = white eyed • XY = male • XX = female

4. Xr Xr XR Xr XR Xr XR Y Xr Y Xr Y Sex-linked Trait Solution: 50% red eyedfemale 50% white eyed male

5. Female Carriers

6. Extensions of Mendelian analysis • Genes follow Mendel’s law of inheritance, but differences in gene action can generate more complex inheritance patterns for phenotypes • Single genes - dominance, codominance, incomplete dominance, overdominance, allelic series, pleiotropy, lethals • Multiple genes - epistasis, polygenic traits • Genes & the environment - sex-influenced traits, environment-dependent gene expression, incomplete penetrance

7. Squares are male Circles are females Colored or filled in shapes are carries of the trait, partially colored shapes are carriers

8. Pedigree analysis • In humans, pedigree analysis is an important tool for studying inherited diseases • Pedigree analysis uses family trees and information about affected individuals to: • figure out the genetic basis of a disease or trait from its inheritance pattern • predict the risk of disease in future offspring in a family (genetic counseling)

9. Today... Pedigree analysis • How to read pedigrees • Basic patterns of inheritance • autosomal, recessive • autosomal, dominant • X-linked, recessive • X-linked, dominant (very rare) • Applying pedigree analysis - practice

10. female male affected individuals Sample pedigree - cystic fibrosis

11. Autosomal recessive traits • Trait is rare in pedigree • Trait often skips generations (hidden in heterozygous carriers) • Trait affects males and females equally

12. Autosomal recessive diseases in humans • Most common ones • Cystic fibrosis • Sickle cell anemia • Phenylketonuria (PKU) • Tay-Sachs disease • For each of these, overdominance (heterozygote superiority) has been suggested as a factor in maintaining the disease alleles at high frequency in some populations

13. Autosomal dominant pedigrees • Trait is common in the pedigree • Trait is found in every generation • Affected individuals transmit the trait to ~1/2 of their children (regardless of sex)

14. Autosomal dominant traits • There are few autosomal dominant human diseases (why?), but some rare traits have this inheritance pattern ex. achondroplasia (a sketelal disorder causing dwarfism)

15. X-linked recessive pedigrees • Trait is rare in pedigree • Trait skips generations • Affected fathers DO NOT pass to their sons, • Males are more often affected than females

16. X-linked recessive traits ex. Hemophilia in European royalty

17. X-linked recessive traits ex. Glucose-6-Phosphate Dehydrogenase deficiency • hemolytic disorder causes jaundice in infants and (often fatal) sensitivity to fava beans in adults • the most common enzyme disorder worldwide, especially in those of Mediterranean ancestry • may confer malaria resistance

18. X-linked recessive traits ex. Glucose-6-Phosphate-Dehydrogenase deficiency

19. X-linked dominant pedigrees • Trait is common in pedigree • Affected fathers pass to ALL of their daughters • Males and females are equally likely to be affected

20. X-linked dominant diseases • X-linked dominant diseases are extremely unusual • Often, they are lethal (before birth) in males and only seen in females ex. incontinentia pigmenti (skin lesions) ex. X-linked rickets (bone lesions)

21. Pedigree Analysis in real life: complications Incomplete Penetrance of autosomal dominant traits => not everyone with genotype expresses trait at all Ex. Breast cancer genes BRCA-1 and BRCA-2 & many “genetic tendencies” for human diseases

22. Pedigree Analysis in real life: complications Sex-limited expression => trait only found in males OR females

23. Pedigree Analysis in real life • Remember: • dominant traits may be rare in population • recessive traits may be common in population • alleles may come into the pedigree from 2 sources • mutation happens • often traits are more complex • affected by environment & other genes

24. What is the pattern of inheritance? What are IV-2’s odds of being a carrier?

25. Sample pedigree - cystic fibrosis What can we say about I-1 and I-2? What can we say about II-4 and II-5? What are the odds that III-5 is a carrier? What can we say about gene frequency?

26. What is the inheritance pattern? What is the genotype of III-1, III-2, and II-3? What are the odds that IV-5 would have an affected son?

27. III-1 has 12 kids with an unaffected wife 8 sons - 1 affected 4 daughters - 2 affected Does he have reason to be concerned about paternity?

28. Breeding the perfect Black Lab How do we get a true-breeding line for both traits?? black individuals = fetch well grey individuals = don’t drool