Lecture 2 - Applying Mendelian Laws

The Punnett square is ideal for predicting the inheritance of _____ traits

one or two

What if you need to track more than 2 traits?

The number of different gametes formula

2^n

(2 = # of alleles so can be changed if theres more alleles)

(n = # of different traits)

how many genotypes in AaBbCcDd, and why would you not use punnett squares to figure this out

Aa Bb Cc Dd = 2^4 = 16 kinds of gametes

Aa Bb Cc Dd * Aa Bb Cc Dd → = 16 x 16 = 256 genotypes’

To do a Punnett square with this cross involving four genes, you would need 16 columns and 16 rows which is much more time consuming

• Cross Aa Bb Cc Dd × Aa Bb Cc Dd

• What proportion of progeny will be AA bb Cc Dd?

•Aa × Aa → 1 ∕ 4 AA

•Bb × Bb → 1 ∕ 4 bb

•Cc × Cc → 1 ∕ 2 Cc

•Dd × Dd → 1 ∕ 2 Dd

So, the expected proportion of AA bb Cc Dd progeny is: 1 ∕ 4 × 1 ∕ 4 × 1 ∕ 2 × 1 ∕ 2 = 1 ∕ 64

Cross Aa Bb Cc Dd × Aa Bb Cc Dd How many progeny will show the dominant traits for A, C, and D and the recessive trait for B?

• Aa × Aa → 3 ∕ 4 A−

• Bb × Bb → 1 ∕ 4 bb

• Cc × Cc → 3 ∕ 4 C−

• Dd × Dd → 3 ∕ 4 D−

So, expected proportion of A− bb C− D− progeny is: 3 ∕ 4 × 1 ∕ 4 × 3 ∕ 4 × 3 ∕ 4 = 27 ∕ 256

How many gametes can an individual with the genotype

AABbCcdd produce?

A)2

B)4

C)8

D)16

In a trihybrid cross AaBbCc x AaBbCc (all three genes assort

independently), what proportion of offspring are expected to

show ALL THREE dominant phenotypes (A_B_C_)?

A)3/64

B)1/64

C)9/64

D)27/64

In a cross AaBbCcDdEe x AaBbCcDdEe (all five genes assort independently), what proportion of offspring are expected to show ALL FIVE recessive phenotypes (aabbccddee)?

A)1/32

B)3/64

C)64/256

D)1/1024

Predicting proportions of progeny from multi-hybrid crosses with Branched line diagrams

From pea plants to humans

Many heritable traits in humans are caused by interaction of multiple genes and so they don't show simple Mendelian inheritance patterns

in humans Even with single-gene traits, determining inheritance pattern in humans can be tricky compared to peas:

• Long generation time

• Small numbers of progeny

• No controlled matings

• No pure-breeding lines

How do we study inheritance in humans?

Pedigree

pedigrees symbols - male, female unspecified (unaffected )

pedigrees symbols - affected, multiple progeny

pedigrees symbols - deceased, consanguinesous mating

pedigrees symbols generations

pedigrees

• Visual representation of the inheritance of a phenotype within a family

• As many generations as possible

• Ideally at least up to grandparents

• Can use Mendel’s Laws to analyze patterns of inheritance

• Dominant vs. recessive traits

Rare trait

individual is assumed to not have the trait allele when no family history is known

From this pedigree: What is the likely genotype of the parents?

A) Both are heterozygote

B) One is homozygote (for recessive allele)

C) One is homozygote (for dominant allele)

Vertical inheritance:

trait appears in every generation

A vertical pattern of inheritance indicates a ____ and why

rare dominant trait

• Every affected person has at least one affected parent

• Two affected parents can produce unaffected children, if both parents are heterozygotes

Example: Huntington disease, The dominant Huntington disease allele produces abnormal Htt protein

Horizontal Inheritance:

trait skips generations

A horizontal pattern of inheritance indicates a_____ and why

rare recessive trait

• Affected individuals can have unaffected parents if they are heterozygous (carriers) for the recessive allele

• All children of two affected parents should be affected

Example: Cystic Fibrosis

The recessive cystic fibrosis disease allele encodes abnormal CFTR protein

From this pedigree: is the trait more likely dominant or recessive?

A) Dominant

B) Recessive

From this pedigree: what is the probability that #4 is a carrier?

From this pedigree: what is the probability that #7 is a carrier?

From this pedigree: If individuals 4 and 7 have a child, what is

the probability that their child will be affected?

A) 1/2

B) 1/3

C) 1/4

D) 1/6

phenotypic variation and simple Mendelian analysis

• Pedigree analysis is built for traits that follow simple Mendelian inheritance

• Many traits exhibit phenotypic patterns that don’t appear to follow Mendel’s rules:

• No definitively dominant or recessive allele

• More than two alleles exist

• Multiple genes involved

• Gene-environment interactions

Extensions to Mendel for single-gene inheritance

Phenotypes in pure-breeding crosses don’t always follow Mendel’s rules…

For a single gene:

• Dominance relationships of alleles

• Genes with more than two alleles

• Recessive lethal alleles

• Genes/Alleles that affect more than one phenotype (pleiotropy)

Dominance relationships of alleles

Dominance is not an intrinsic property of alleles

What makes an allele dominant?

• The phenotype of the heterozygote determines the dominance relationship between two alleles

• Dominance is a description of how two alleles interact to produce a phenotype, not an inherent property either allele carries around independently

The phenotype of the ___ defines the dominance relationship of two alleles

heterozygote

Complete dominance:

Hybrid resembles one of the two parents

Incomplete dominance:

Hybrid is intermediate phenotype of parents •

Codominance:

Hybrid shows traits from both parents

Flower color in snapdragons is an example of __ dominance

incomplete

➢ Crosses of pure-breeding red with pure-breeding white results in all pink F1 progeny

➢ Phenotype ratios reflect the genotype ratios

in radishes, root color shows incomplete dominance: RR = red, Rr = purple, rr = white. A purple radish plant (Rr) is crossed with a white radish plant (rr). What is the expected phenotypic ratio of red : purple : white among the offspring?

A) 1 red : 2 purple : 1 white

B) 1 purple : 1 white

C) 1 red : 1 white

D) 3 purple : 1 whit

Genes with more than two alleles

Dominance relationships are only meaningful when examining pairs of alleles

Dominance isn't a property one allele carries in isolation example

In lentils, the seed coat pattern dominance series is: A plant heterozygous for marbled and clear is crossed with a plant heterozygous for spotted and clear. What is the probability that an offspring shows the marbled phenotype?

A) 1/4

B) 1/2

C) 3/4

D) 1/8

In the ABO blood type system, genotype I A i produces type A blood, and genotype I AI B produces type AB blood (both antigens present). Based on this, which statement about the I A allele is correct?

A) IA is codominant with both i and IB

B) IA is recessive to both i and IB

C) IA is dominant over i, but codominant with IB

D) IA is always dominant, regardless of pairing

ABO blood types

Medical implications of multiple alleles

Histocompatibility antigens

– HLA-A, HLA-B, & HLA-C in humans

– Each with 400-1200 alleles, all codominant

– Can lead to rejection of organ transplants

_____ are the source of new alleles

Mutations

Mutations:

chance alterations of genetic material that arise spontaneously

• If mutations occur in gamete-producing cells, they can be transmitted to offspring

Allele frequency

the percentage of the total number of gene copies for an allele in a population

• Wild type (+) alleles are the most common in the population

• Mutant alleles are present at <1%

Monomorphic genes:

have only one wild-type allele

Polymorphic genes:

have more than one wild-type allele, which are usually called common variants

Recessive lethal alleles

Albino corn seedlings (gg) have a recessive mutation in a gene needed to produce chlorophyll -> dead within weeks'

Only one phenotype survives to maturity

• Adult population: All green

Recessive lethal alleles - Curly of Oster (CyO) mutation in Drosophila

• C is dominant to c for wing shape, but recessive to c for lethality

• "dominant" and "recessive" here describe two different phenotypes

Recessive lethal alleles - agouti gene

The Ay allele of agouti gene causes yellow hairs

• Crossing two yellow mice (Ay A) results in 2:1 (yellow : agouti) ratio

Ay is dominant to A for hair color, but is recessive to A for lethality

In Manx cats, the tailless allele (M) is dominant for tail phenotype, but homozygous (MM) embryos die before birth. If a normal-tailed cat (mm) is bred with a tailless cat (Mm), what is the expected ratio of tailless to normal-tailed kittens?

A) 3:1

B) 2:1

C) 1:1

D) 1:2:1

Pleiotropy:

the phenomenon of a single gene determining several distinct and seemingly unrelated characteristics

Genes/Alleles that affect more than one phenotype (pleiotropy)

Example: ER localized HSP90 in Arabidopsis (Athsp90.7) has a pleotropic effect on plant growth (involved in many processes including fertility, stress responses, and survival)

Homozygotes for mutant allele (nonfunctional protein) exhibit different distinct phenotypes

Most proteins are expressed in a variety of tissues and are involved in multiple biochemical processes → mutations in a gene have a good chance of creating pleiotropic effect

Pleiotropy of sickle-cell anemia:

The lethal yellow (Ay ) mutation in mice causes yellow coat color, obesity, and diabetes (all traced to ectopic overexpression of the agouti gene product) AND embryonic lethality in homozygotes (traced to disruption of a separate, neighboring gene called Raly, destroyed by the same deletion). Which part of this phenotype set is a genuine example of pleiotropy?

A) Only the embryonic lethality

B) All four effects together (coat color, obesity, diabetes, and lethality)

C) Only the coat color, obesity, and diabetes effects

D) None of it