1. Human genetics How to determine inheritance of a trait in humans
Can’t (shouldn’t) mandate breeding partners
Low numbers of offspring.
Pedigrees
Follow inheritance of trait in families
Compare results to other families
Draw conclusions.

2. Key to pedigrees

3. Pedigree sample-1 *Look for things you know must be true.
Look at inheritance of trait expressed by shaded individual.
You KNOW that it can’t be dominant because at least 1 of the parents would also have to show that phenotype.

4. Pedigree sample-2
Beware of things that seem logical but might NOT be true.
The Shaded trait is dominant.
“A” dominant, “a” recessive
The mother must be aa.
The father, however, may or may not be homozygous:
If the father is AA, you would expect all offspring to be Aa (AA x aa = Aa); this is what appears to be true.

5. continued
BUT, if the father is Aa, the odds for each child showing the dominant phenotype is 50:50.
Just like you can flip a coin 3 times and get heads each time, you could get 3 children that are all Aa, showing the dominant phenotype.
The father COULD be Aa. Likely? No. Possible? Definitely.

6. Pedigree problem
A and a are alleles. Which is shaded? What are the genotypes?
Find the sure things first.
II 6 must have a recessive trait, being unlike both parents (who must be heterozygous).

7. Genetic Notation -eukaryotes
Dominant: upper case; recessive: lower case.
From Plant studies
Based on dominant/recessive relationships
Letter describing trait: P p for Purple, white alleles

8. Genetic Notation –eukaryotes-2
From animal studies; based on “wild type” concept
Wild type is most common allele, indicated by “+”
Example: e+/ e where e+ is wild type, slash separates alleles from homologs
Example: Wr+/ Wr shows mutant phenotype because Wr is a dominant mutant allele
Multiple alleles: R1 & R2; IA & IB;
Bacterial notation different

9. Mutation and phenotype
Mutations are the source of new alleles
A new allele may result in a new phenotype because of changes in enzyme activity
Enzyme usually has decreased or no activity
Enzyme may have increased activity
usually, change in a regulatory gene
Enzyme may be unaltered despite change in DNA
Allele only at DNA level, no other phenotype

10. Alterations to Mendel Incomplete or partial dominance Codominance
Multiple alleles
Lethal alleles
Gene interactions
Sex-linked, sex-limited, & sex-influenced
Effect of environment
Extranuclear inheritance

11. Multiple genes
Sometimes a phenotype is controlled by more than one gene
Different from multiple alleles of same gene!!
Gene products don’t necessarily directly interact.
Genes may code for enzymes in a pathway
Cascade of gene during development
Epistasis: a gene (or gene pair) masks or modifies the expression of another gene (or gene pair).

12. Epistasis: gene interaction that perturbs normal Mendelian ratios
Example: interaction between two genes in the pathway for pigment production, C and P
C, P = dominant; c, p = recessive.
Because both genes are needed, if individual is homozygous recessive for either gene, no color.
CcPp, all colored in F1
CcPp x CcPp 9:7 phenotypic ratio
Do the Punnett square and see
Independent assortment still applies
Various interactions produce different ratios.

13. Epistasis example: Bombay phenotype
In the ABO blood groups, A and B are codominant.
How can the person in this pedigree be type O (IO IO)?

14. Epistasis example: explanation
A second gene, Ih codes for the base sugar chain to which the A and B sugars are added. A rare mutation Ih Ih prevents proper formation so that the A and B sugars cannot be added even though the enzyme for doing that is being made. (Diagram next slide)
A second gene is masking the normal phenotype.

15. Molecular explanation