Variation, probability, and pedigree

1. Variation, probability, and pedigree • Gamete production is source of variation and genetic diversity, an advantage of sex. • As a result of segregation and independent assortment, lots of combinations possible. • 2n possibilities exist for diploids where n = haploid number of chromosomes • In humans, this is 8 million different gametes • Crossing over during meiosis creates even more combinations of genetic information • This diversity important in evolution, survival.

2. Product law • Product law used to calculate odds of an outcome from independent events • Flip a coin: heads or tails, 50:50 chance (1/2) • Flip a coin 3 times, get 3 heads; the next flip, there’s still a 50:50 chance of getting a head. • The chance of getting 4 heads in a row: • ½ x ½ x ½ x ½ = 1/16 the product law. • Odds of round, yellow seeds in a cross of Ww GG x Ww gg: ¾ x 4/4 = 3/4

3. Sum Law • The sum law: outcomes of events are independent, but can be accomplished in more than one way. Flip a penny and a nickel: odds of 1 heads and 1 tails? There are 4 possible outcomes from this flip. 1 head, 1 tail can be from the penny being heads (odds 1/4), but also from the nickel (1/4): ¼ + ¼ = ½

4. 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.

5. Key to pedigrees

6. Pedigree sample-1 • 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. *Look for things you know must be true.

7. 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.

8. 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.

9. Pedigree problem from text 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).

10. 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 • 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;

11. 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

12. 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

13. Incomplete or partial dominance One allele only partially masks the other. Half as much enzyme makes half as much pigment. Phenotypic ratio is the same as genotypic: 1:2:1 www.people.virginia.edu/ ~rjh9u/snapdragon.html

14. Partial dominance-2 • Partial dominance is not common • A molecular phenotype showing partial dominance is more common • One allele instead of 2 is producing enzyme, so on a gel, a protein band is half as intense.

15. Codominance • M and N blood groups: LM LN • Glycoprotein on blood cell surface • If one of each allele, both expressed. • Phenotype = genotype, essentially • Heterozygote cross: shows 1:2:1 ratio http://boneslab.chembio.ntnu.no/Tore/Bilder/BlodMN.jpg

16. Multiple alleles • In peas, Mendel following the inheritance of two contrasting traits, e.g. purple vs. white flowers • Often, more than two alleles for a trait exist. • Study of multiple alleles requires a population! • In diploid organisms, an individual can only have a maximum of two alleles. (2 different alleles) • In populations, many different alleles may be present. • Classic example: the ABO blood group system

17. ABO Blood groups Series of sugars added to cell lipid creates trait. Genotypes include: AA, AO = type A BB, BO = type B OO = type O AB = type AB where A and B are co-dominant, O is recessive, and the blood type is the phenotype. http://science.uwe.ac.uk/StaffPages/na/abo_ho2.gif

18. Lethal alleles • In genetic crosses, information is obtained by examining the phenotype of the offspring. • In some instances, the phenotype is lethal • Lethality may present itself late in life (Huntington Disease) or may result in no offspring. • Example: Fur color in mice: Agouti on left, yellow on right. http://www.cumc.columbia.edu/news/in-vivo/Vol1_Iss21_dec18_02/img/obesity-mice.jpg

19. Lethal alleles-2 • If certain genotypes are lethal, results of a cross may be quite confusing. • Agouti x agouti = all agouti • Yellow x yellow = 2/3 yellow, 1/3 agouti • Agouti x yellow = ½ yellow, ½ agouti • 2:1 ratio is tip-off that something odd happens • Homozygous for yellow is lethal, so that genotype is NOT represented. • For lethality, yellow allele acts as recessive. • For coat color, yellow allele acts as dominant • A = agouti, Ay = yellow. Heterozygote is yellow.

20. Complex inheritance and dihybrid crosses • Book example: inheritance of simple trait and multiple allele trait: albinism and ABO • Crossing of heterozygotes • Mm (albinism) and AB (blood type) • Assume independent assortment • Simple trait shows 3:1 ratio, co-dominant trait shows 1:2:1 ratio • Phenotypic classes in offspring no longer 9:3:3:1 • Actually come out 3:6:3:1:2:1 • Complex inheritance produces odd ratios.

21. Really good practice problems • http://www.biology.arizona.edu/mendelian_genetics/mendelian_genetics.html • Do all the problems from the links “Monohybrid cross” and from “Dihybrid cross”.