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Simple statistics used in genetics.!

product rule - if two events are independent, the probability of both


occurring is the product of each of them occurring. !
p(a and b) = p(a) x p(b).!
p(RRYY) = p(RY) p(RY) = (1/4)(1/4) = 1/16!
sum rule - for two exclusive events, the probability for either
occurring is the sum of them both. !
p(a or b) = p(a) + p(b).!
p(RRyy or Rryy) = 1/16 + 2/16 = 3/16!

1!

Clicker Q 5: Multiple Genes!


P !RR yy PP x rr YY pp!

F1 ! !Rr Yy Pp (round, yellow, purple)!

If Rr Yy Pp were selfed, what proportion of the progeny would be


homozygous recessive for all three genes?!
1." 1/8!
2." 1/16!
3." 3/16!
4." 1/64!
5." 3/64!
6." 9/64!
Clicker Q 6: Multiple Genes!
P !RR yy PP x rr YY pp!

F1 ! !Rr Yy Pp (round, yellow, purple)!

If Rr Yy Pp were selfed, what proportion of the progeny would have a


dominant phenotype for R and Y, but recessive for P?!
1." 1/8!
2." 1/16!
3." 3/16!
4." 1/64!
5." 3/64!
6." 9/64!

Clicker Q 7: Multiple Genes!


P !RR yy PP x rr YY pp!

F1 ! !Rr Yy Pp (round, yellow, purple)!

If Rr Yy Pp were selfed, what proportion of the progeny would have a


dominant phenotype for one of the genes, but be recessive for the other
two genes?!
1." 1/8!
2." 1/16!
3." 3/16!
4." 1/64!
5." 3/64!
6." 9/64!
Clicker Q 8: Multiple Genes!
P !RR yy PP x rr YY pp!

F1 ! !Rr Yy Pp (round, yellow, purple)!

If Rr Yy Pp were selfed, what proportion of the progeny would breed


true?!
1." 1/8!
2." 1/16!
3." 3/16!
4." 1/64!
5." 3/64!
6." 9/64!

Mendelian Analysis in Humans!


Most traits are affected by more than one gene and cannot be
analyzed using simple Mendelian genetics.!
Many single gene traits that can be followed cause rare diseases,
rather than common phenotypes.!
Human genetics is not straight forward:!
No pure breeding humans.!
Generation time is long.!
No controlled matings.!
Siblings rarely mate to generate F2.!
Small family size.!
How can one study human genes that cause human diseases?!
Geneticists make use of the variation that already exists in the
population.!
Pedigree analysis. Rare traits can be studied by carefully
analyzing families that are affected. In other words, the trait may
be rare in the population but common in a particular family.!
Female!

Male! I!
Unknown Sex!

II!
Individual with a trait! 1 2 3 4 5!

III! 2!
Heterozygous!

Deceased!
Consanguineous!
4! Number of children ! mating!
of indicated sex! Carrier (heterozygous)!
Pedigree of a rare
recessive phenotype. !
A is dominant allele.!
a is recessive allele.!
a is rare.!

Cystic Fibrosis!

- Afflicted individuals often die


by the age 20.

- Prevalent in Northern European


populations (carrier frequency
can be as high as 1/20)

- Gene encodes chloride transport


channel protein

- May confer resistance to cholera


toxin
Clicker Q 9: Pedigree Analysis in Humans!
Cystic fibrosis is a rare recessive disorder. Jack whose brother has the disease
marries Jill whose aunt has the disease. !

If they have one child, what is the probability that the child will have cystic
fibrosis?!
A.! 2/3 x 2/3 x 1/2 x 1/4 = 1/18!
B.! 1/2 x 2/3 x 1/2 x 1/4 = 1/24!
C.! 1/2 x 1/2 x 1/2 x 1/4 = 1/32!
D.! 2/3 x 2/3 x 2/3 x 1/4 = 2/27!
E.! None of above.!

Clicker Q 10: Pedigree Analysis in Humans!


Cystic fibrosis is a rare recessive disorder. Jack whose brother has the disease
marries Jill whose aunt has the disease. !
b) If their first child has cystic fibrosis, what is the probability that their
second child will have cystic fibrosis?!
A.! 2/3 x 2/3 x 1/2 x 1/4 = 1/18!
B.! 1/2 x 2/3 x 1/2 x 1/4 = 1/24!
C.! 1/2 x 1/2 x 1/2 x 1/4 = 1/32!
D.! 2/3 x 2/3 x 2/3 x 1/4 = 2/27!
E.! None of above.!

?!
Pedigree Analysis in Humans!
Cystic fibrosis is a rare recessive disorder. Jack whose brother has the disease
marries Jill whose aunt has the disease. !
c) If their first and second child has cystic fibrosis, what is the probability
that their third child will have cystic fibrosis?!

d) If their first child has cystic fibrosis, what is the probability that of their
next three children, two will be carriers and the other affected?!

?!

Extension on Mendel!
Incomplete Dominance!

Incomplete (or
partial) dominance:
Phenotype of
heterozygous hybrid
is intermediate
between
homozygous parents.
Extension on Mendel: Incomplete Dominance!

•"Genotypic ratio is 1:2:1 and so is the phenotypic ratio.


•"Mendel’s laws are still valid at the genotypic level.

Molecular Explanation of one example of incomplete


dominance!
Precursor Red pigment Pigment forming
enzyme is present in
limiting quantities, so
Red pigment forming enzyme
A = Dominant allele makes a normal enzyme having more makes the
a = Recessive allele makes a defective one flowers more red.

A
A
A
a
a
a
Extension on Mendel: Co-Dominant Alleles!
phenotypes of both alleles are observed
in the heterozygotes

~ Complete dominance!

~ Codominance!

~ Incomplete dominance!
Extension on Mendel: Multiple Alleles!
Multiple alleles!
Coat color in guinea pigs!
CC = black ! ! !Ccd = black!
k k
c c = sepia ! ! !ckca = sepia!
cdcd = cream! ! !!
caca = albino!

Coat color in guinea pigs have a hierarchy of dominance:!


C > ck > cd > ca!

Clicker Q 11: Multiple Alleles!


What is the color (phenotype) of a cdca guinea pig.!
A."Black!
B."Sepia!
C."Cream!
D."Albino!
E."Can#t tell.!

Clicker Q 12: Multiple Alleles!


Multiple alleles!
Coat color in guinea pigs!
CC = black ! ! !Ccd = black!
ckck = sepia ! ! !ckca = sepia!
d d
c c = cream! ! !!
a a
c c = albino! Ccd! ckca!
Hierarchy of dominance:!
C > ck > cd > ca!
?!

What ratio of color (phenotype) is the F1 guinea pig progeny?!


A." 2 Black: 1 sepia: 1cream!
B." 3 Black: 1 sepia!
C." 2 Black: 2 cream!
D." 1 Black: 1 sepia: 1 cream: 1 albino!
E." Can#t tell or don#t know.!
Clicker Q 13: Multiple Alleles!
Multiple alleles!
Coat color in guinea pigs!
CC = black ! ! !Ccd = black!
ckck = sepia ! ! !ckca = sepia!
d d
c c = cream! ! !!
a a
c c = albino!
Hierarchy of dominance:! Black x sepia!
C > ck > cd > ca!

2 black + 1 sepia + 1 albino!

What are the genotypes of the parents?!


A." CC x ckck!
B." Cca x ckck!
C." CC x ckca!
D." Cca x ckca!
E." Can#t tell or don#t know.!

ABO Blood Group!


Multiple alleles and Incomplete Dominance!
ABO Blood Group!
There are three alleles: IA IB and i!
IA and IB are co-dominant; i is recessive.!
Phenotype !Genotype!
O ! !ii! AB! AB!
A ! !IAIA or IAi!
B ! !IBIB or IBi!
AB ! !IAIB! B!
A!

?!
What are the possible phenotypes of the
child?!
Clicker Q 14: ABO Blood Group!
Multiple alleles and Incomplete Dominance!
ABO Blood Group!
Phenotype !Genotype!
O ! !ii!
A ! !IAIA or IAi!
B ! !IBIB or IBi!
AB ! !IAIB!

There are 4 children who have the following blood types; A, B, O, AB!
These children belong to 4 sets of parents who are AB x O; A x O; A x AB and O x O.!
As best as you can, match up the children with their parents.!

! !#1 ! !#2 ! !#3 ! !#4!


AB x O ! !AB ! !AB ! !B ! !AB or B!
AxO ! !O ! !A ! !A ! !A!
A x AB ! !B ! !B ! !AB ! !AB or B!
OxO ! !A ! !O ! !O ! !O!

Extension on Mendel: Complementation!


Genes Affecting the same character!
P !white x white!

F1 ! purple!

F2 !9 purple : 7 white!
These genes have complementary action. !
Complementation: 2 or more genes necessary to give a function.
If they complement they are different genes. If they fail to
complement they are the same gene.!
The complementation test.!
If two mutants
complement, they
are in different
genes.!

If two mutants fail


to complement,
they are in the
same gene.!
Extension on Mendel: Epistasis!
Genes Affecting the same character!
P albino x black!

F1 agouti!

F2 9 agouti : 3 black : 4 albino!

Epistasis - one gene interferes with or masks another gene.!

Extension on Mendel: Redundant Genes!

Genes Affecting the same character!


Shepherds Purse!
Round fruit x Narrow fruit!

! !all round!

15 round : 1 narrow!

Redundant genes are usually caused by a gene duplication.!


Extension on Mendel: Lethal Alleles!
Lethal Alleles - All biological functions are under the control of
genes, some genes are essential for viability.!
Yellow gene of mice.!
!Y/y x y/y!
!y/y and Y/y in 1:1 ratio!

!Y/y x Y/y!
!2 yellow : 1 normal (expect 3:1)!
backcross yellow and they look like heterozygote.!
Look at pregnant females and find 1/4 embryos are dead.!
Y is dominant for yellow hair color!
Y is a recessive lethal (Y/Y individuals die).!

Clicker Q 15: Lethal Alleles!


You isolate a recessive lethal allele of the dead gene in Drosophila
melanogaster. This imaginary gene maps on the X chromosome.
A female heterozygous for dead (d+/d) is phenotypically wild type
but males carrying the recessive allele (d/Y) are never found, the
d allele has a recessive lethal phenotype. A female heterozygous
for dead is mated with a wild type male.!

What is the ratio of males to females among the progeny of the


above cross?!
A. 3 males : 1 female!
B. 2 males : 1 female!
C. 1 male : 1 female!
D. 1 male : 2 female!
E. 1 male : 3 female!
Extension on Mendel: Penetrance!
PENETRANCE = % with expected phenotype for a given
genotype.!
Examples of 100% penetrance: Mendal#s Peas, ABO!
Incomplete penetrance (<100%)!
Retinoblastoma (Autosomal Dominant).!
Huntington#s Disease. “Woody Guthrie” Disease. Autosomal
dominant.!
Neurological defects with old age (40s to 80s).!

Extension on Mendel: Expressivity!


EXPRESSIVITY = variation in intensity of phenotype for given
genotype.!
phenylketonurea (PKU) - rare recessive allele in humans. PKU
individuals cannot convert phenylalanine to tyrosine. Severe
mental retardation.!
Connecticut state university!
!" Phenotype controlled by many genes with many alleles.! Crow, 1997 Genetics 147:1!
!" Produce a continuum of phenotypes. !
These are called continuous traits, or quantitative traits, because they vary over
a wide range of values.!

All of the mechanisms that we discussed contribute to continuous variation.


Complex dominance relationships, multiple alleles, and multiple genes
interacting in complex ways determine the genetic diversity of life. !