Bio D137 - Midterm 1

What is the expected concordance for dizygotic twins for a recessive trait?

What is the expected concordance for dizygotic twins for a recessive trait?

25% (Aa x Aa = ¼ chance of aa)

What is the concordance for monozygotic twins if the trait is fully genetic?

100%

What is the expected concordance for dizygotic twins if the trait is dominant?

50%

What is the expected difference between CMZ and CDZ if the trait is fully environmental?

0

What fraction of a trait is genetically caused if a trait is suspected recessive?

(CMZ - CDZ) / 75

What is truncate selection?

The children are the probands, infer parental genotype from children

What is non-truncate selection?

Parent genotype is known (no bias)

What is complete truncate selection?

When you randomly select families, with the probability of finding families with 1 affected children is equal to the probability of finding families with multiple affected kids

What is incomplete truncate selection?

The families are within the same population (not fully randomly selected), so the probability of finding families with multiple affected kids is higher

What is the tyrosine metabolism pathway?

Catabolic pathway that breaks down amino acid phenylalanine.Wha

What cells are keratin present in?

Only keratinocytes

What cells is the tyrosine metabolism pathway present in?

Every cell

What is mutated to cause phenylketonuria (PKU)

phenylalanine hydroxylase enzyme that converts phenylalanine to tyrosine

What mechanism is phenylketonuria (PKU) inherited?

autosomal recessive

What is the most common “in born error” in metabolism?

Phenylketonuria (PKU)

What is the effect of phenylketonuria (PKU)?

Toxic buildup of phenylalanine in neurons because cell isn’t able to convert it to tyrosine which causes mental retardation

Best treatment for phenylketonuria (PKU)

Diet low in phenylalanine

What is the effect of alkaptonuria?

Buildup of dark pigment in eyes, urine, and cartilage

What mutation causes alkaptonuria?

Mutation in homogentisate oxidase enzyme

What disease led to the initial “one gene, one enzyme” hypothesis?

alkaptonuria

What mechanism is alkaptonuria inherited through?

autosomal recessive

What happens in tyrosinemia?

Mutation leads to buildup of tyrosine

How can you reduce the severity of tyrosinemia? What type of tyrosinemia does this work for?

Diet of low tyrosine (only works for Type II, NOT I)

What is the most abundant type of protein?

Structural

What are the three types of proteins?

Structural, regulatory, and catalytic

Give an example of a structural protein and its structure?

Keratin; long dimer strand of Type I and Type II keratins

What indicates if a disease is a keratin mutation?

Name contains “kerat” or “Bullosa”W

What type of mutation are keratin mutations typically? Why?

Autosomal dominant; since keratin is a dimer, 1 bad copy disrupts dimerization with other

Example of regulatory protein

Fibroblast Growth Factor (FGFs)

How are diseases like Dwarfism and craniosynostosis caused?

Overactive FGFs that signal to kinases too early for the fusion of sutures

What is scurvy? Is there a genetic basis to it?

Vitamin C deficiency; genetic basis is from defect in L-gulonolactone oxidase (converts glucose —> absorbic acid)

What are the three assumptions of Mendel’s 1st law?

1) Equal segregation to gametes

2) Random union at fertilization

3) Reciprocity

What are the two main categories of Non-Mendelian inheritance?

1) Lack of Equal Segregation

2) Lack of Reciprocity

Give 3 examples of lack of equal segregation that would cause deviations from Mendelian inheritance?

1) multigenic = more than 1 gene contributes

2) incomplete penetrance = same mutation doesn’t always have same severity

3) environmental

Give 2 examples of lack of reciprocity that would cause deviations from Mendelian inheritance?

1) sex-linked traits

2) maternal effects = things deposited by mother into egg affect it more than father

What mode is Parkinson’s inherited through?

Recessive

What mode is Huntington’s disease inherited through?

autosomal dominant

Define penetrance

proportion of individuals carrying allele AND showing the phenotype

Define expressivity

How extreme someone with an allele exhibits the phenotype

What is the phenotypic trait of ptosis?

One eye lowered

Give an example of recessive epistasis

Fur color in dogs (B and E)

If ‘ee’ genotype, fur color is yellow regardless of B genotype.

Give an example of dominant episatsis

Squash color (A and B)

-Normally, B_ makes yellow squash and bb makes green colored squash

-However, ‘A_’ is epistatic to B, preventing leading to only white fruit regardless of B allele

What ratios are found in a cross with two heterozygotes with recessive epistasis?

9:3:4

What ratios are found in a cross with two heterozygotes with dominant epistasis?

12:3:1

Name 3 X-linked recessive disorders

1) Duchenne Muscular Dystrophy

2) Colorblindness

3) Hemophilia

Name an x-linked dominant disorder

Fragile X

Name a Y-linked disorder

Sex reversals from SRY

What is Trisomy 21?

Down syndrome

What does LOD stand for?

Logarithm of the Odds

What are the 4 reasons to use LOD?

1) don’t know parental linkage of alleles

2) don’t know phase of linked alleles

3) have to pool individuals w/ different genotypes

4) various families with different sizes

How to calculate LOD score?

log(prob linked/prob independent) = Z score

log((1-theta)^NRC * theta^RC/0.5^(total # offspring))

How to calculate LOD score if phase is unknown?

Score once assuming coupling and once assuming replusion then divide by 2

What LOD score is necessary to accept linkage? Reject linkage? Inconclusive?

LOD > 3 = linked

LOD < -2 = independent

-2 < LOD < 3 = inconclusive

Define heterogeneity

different genotypes/mutations can cause the same phenotype (ex: Aa and AA cause same phenotype)

What does dosage compensation do?

Equalizes dosage of X-linked genes

What is X inactivation?

One of two chromosomes in each somatic cell shut down randomly

Define barr body

When an X-chromosome is inactivated, it condenses (preventing its expression) and plasters itself against the nucleus

What % of genes escape X-inactvation? How does this happen?

~15% escape inactivation. Happens because levels of XIST (a long non-coding RNA that binds to DNA to shut it down) vary across the chromosome

How does sex determination modes differ across mammals, birds, reptiles/fish, and flies?

Mammals = XY vs. XX

Birds = ZZ (males) vs. ZW (females) - females hemizygous, not males

Reptiles + fish = temperature + aromatase (presence of estrogen)

Flies = ratio of X chromosomes to autosomes

Primary sex determination in mammals

Dependent on what gonads differentiate into (initially bipotential gonads)

Become testes in males, ovaries in females

What gene is the testis determining factor? What chromosome does it appear on?

SRY gene, Y chromosome - necessary but not sufficient to become male

What two major hormones do testes produce

Anti-Mullerian hormone (AMH) and testosterone

What is secondary sex determination in mammals?

STEROID HORMONES trigger changes in genitalia, body size, vocal chords, facial hair

What two ducts does the bipotential gonad make? Which is preserved in male differentiation and which is preserved in female differentiation?

Mullerian (female) and Wolffian (male) - become exit routes for eggs and sperm respectively

SOX9 gene

Autosomal testis-determining factor

-turns gonads into testes but not sufficient for fertility

DAX1 gene

testes-suppressing gene

-antagonizes SRY + SOX9

-co-expressed with SRY then only stays on in ovaries

WNT4 gene

ovary determining gene

-activates DAX1 and inhibits SOX9

Sex determination in Drosophila flies based on….

ratio between X chromosomes to autosomes (female determinants on X, male determinants on autosomes)

Sxl (sex lethal) gene in drosophila

regulates somatic sex determination by regulator transformer (tra)

-Sxl protein does alternative splicing of exon to create “male” or “female” product

Dxs (double sex) in drosophila

Transcription factor for male/female organs

How do humans impact frog sex determination?

Chemicals like herbicides and pesticides (namely atrazine) degenerate testes in frogs —> forced feminization

What is missing in simple Mendelian pedigrees that makes LOD superior for linkage mapping?

phase of parental alleles to know which children are recombinants and which aren’t

How are chiasmata and recombination frequency related

RF = # chiasmata / 2

How to calculate % offspring with certain traits when given only parental genotypes, phase alleles, and map units

Map units = recombination frequency

If you want parental of two alleles, use 1-RF for those two genes. If you want recombinant, use RF. Divide by 2 for 50% chance of inheriting the correct chromosome.

Ex: (1-0.1) * 0.32 / 2 = 11.4% inheriting all desired traits