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.

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

Sum Law Flip a penny and a nickel: odds of 1 heads and 1 tails? 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

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.

Key to pedigrees

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.

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.

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.

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).

Modification of Mendel Definitions and terms from Chap. 4 Autosomes vs. sex chromosomes Wild-type: “normal”, usually dominant Dominant does NOT mean most common Examples: e+/ e where e+ is wild type, slash separates alleles from homologs Lower case “e” means recessive Wr+/ Wr shows mutant phenotype because Wr is a dominant mutant allele R1 & R2; IA & IB; leu-; etc. DnaA is a protein, dnaA is the gene!!

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

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

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

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.

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

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

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

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

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.

Complex inheritance and dihybrid crosses Book example: inheritance of simple trait and multiple allele trait: albinism and ABO Crossing of heterozygotes (blood group AB) 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.