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

3. 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 XR Xr Y

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

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. Sample pedigree - cystic fibrosis
female
male
affected individuals

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. ex. achondroplasia (a sketelal disorder causing dwarfism)
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. ex. Hemophilia in European royalty
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