1Variation, 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.

2Product 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

3Sum 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

4Human 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.

5Key to pedigrees

6Pedigree 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.

7Pedigree 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.

8continued

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.

9Pedigree 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).

10Modification 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!!

11Mutation 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

12Alterations to Mendel

• Incomplete or partial dominance

• Codominance

• Multiple alleles

• Lethal alleles

• Gene interactions

• Sex-linked, sex-limited, & sex-influenced

• Effect of environment

• Extranuclear inheritance

13Incomplete or partial dominance

www.people.virginia.edu/ ~rjh9u/snapdragon.html

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

14Partial 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.

15Codominance

• 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

16Multiple 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

17ABO Blood groups

http://science.uwe.ac.uk/StaffPages/na/abo_ho2.gif

Series of sugars added to cell lipid creates trait.Genotypes include:AA, AO = type ABB, BO = type BOO = type OAB = type AB where A and B are co-dominant,O is recessive, and the blood type is the phenotype.

18Lethal 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

19Lethal 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.

20Complex 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.