Pedigrees + Linkage

X- Linked Recessive

- Most males are affected

- Never passes male-to-male

- Female carriers

- Affected females must have an affected father

- Present exclusively in males

X-Linked Dominant

- Never passes from father to son

- Affected males: all daughters affected, no sons

- Affected females: half or more children

Autosomal Dominant

Most affected are heterozygous, homozygous for this trait is lethal in utero

Autosomal Recessive

Carriers have Aa, which can be a case of inbreeding.

Y-Linked

- ONLY males affected

- male-to-male, mutation or incomplete penetrance

Mitochondrial Disease

- Males and females affected

- Males can't transmit

- The affected male must have an affected mother

Incomplete Dominance

- The heterozygote is midway between both phenotypes

- dosage-dependent effect

Incomplete Penetrance

- With the genotype but aren't affected by disease

Variable Expressivity

- all have the same genotype, all manifest some symptoms, but not uniformly

Multigenic

- Involves two or more genes

Calculating Risk (One Child)

P1 x P2 x Child (likelihood of a given genotype)

Predicting Risk for Multiple Children

A couple has 4 children, the likelihood that 3 are affected: 4!/3!1! x 1/4 x 1/4 x 1/4 x 3/4

How related are second cousins?

5th degree of related (6 individuals in loop - 1)

(1/2)^(degree of relatedness) = 1/32 alleles in common

1/32*2 = 1/64 coefficient of inbreeding of child (F)

How related are first cousins?

3rd degree of related (4 individuals in loop - 1)

(1/2)^(degree of relatedness) = 1/8 alleles in common

1/8*2 = 1/16 Inbreeding child coefficient

How related are uncle/niece?

2nd degree of related (3 individuals in loop - 1)

(1/2)^(degree of relatedness) = 1/4 alleles in common

1/4*2 = 1/8 inbreeding child coefficient

How related are first cousins once removed?

4th degree related (5 individuals in loop - 1)

(1/2)^(degree of relatedness) = 1/16 alleles in common

1/16*2 = 1/32 inbreeding child coefficient

What is the expected linked genotype ratio between two heterozygotes?

9:3:3:1

Where do non-parentals come from when crossing different chromosomes?

Independent assortment in Meiosis I

Where do non-parentals come from on the same chromosome?

recombination

What is the expected ratio of genotypes if the genes are unlinked?

1:1:1:1

How to find frequency of recombinants

recombinant/ recombinant + parentals

Coupling hetrozygote

Dominant alleles on the same chromosome (RL/rl)

Repulsion heterozygote

dominant and recessive alleles on different chromosomes (Rl/rL)

When is map distance unlinked?

>50 cM

How is map location and distance determined?

- Find which pair has a single cross for each interval

- Add up the total for relevant air plus the double crossovers

- Divide by the total number

- Multiply by 100 to convert into centiMorgans

How do you determine gene order?

- Put the furthest apart on the outside and work from one side to another

- Start from one side and find the shortest interval from the outside gene on that side

- Put the gene and the distance closest to the edge you are working from

- Repeat steps 2 through 5 until you get to the other end

coefficent of coincidence

ratio of observed double crossovers to expected double crossovers

Interference

A crossover in one region can physically impede a nearby crossover

What recombination frequency is most accurate for a two-point cross?

<20cM

What recombination frequency is most accurate in a three-point cross?

>20cM