BIOL 207 - Post Midterm Content

lectures from Dr. Clare Venney; modules 12-17 (Sex determination and sex-linked characteristics, Pedigree analysis, applications, and genetic testing, Population genetics, Quantitative genetics, Gene interactions at multiple loci, Chromosome variation); no wooclap practice questions included

What is sex vs gender?

Sex - anatomical and physiological phenotype, seen in most organisms

Gender - social construct based on identity, only found in humans

What is environmental sex determination (ESD)?

Sex determined by environment, no chromosomes

What types of organisms show environmental sex determination (ESD)?

Reptiles, fish, plants

How is environmental sex determination (ESD) seen in sea turtles?

Egg temperature determines offspring sex:

• Warm (> 31°C) → female

• Cold (< 27.7°C) → male

• 27.7°C to 31°C → mixed sex

How is environmental sex determination (ESD) seen in green spoonworms?

• Females produce bonellin as protection from threat species:

• Offspring are tiny enough to move with the current:

  • Sucked into female, contact with bonellin → male

  • No contact with bonellin → female

Why would environmental sex determination (ESD)? evolve the way it did in green spoonworms?

Any larvae touched by a female will develop into a potential mate → increases chances of reproduction in low population densities

How is environmental sex determination (ESD) seen in clownfish?

Juveniles are undifferentiated until social cues shift them to males

• Males can grow and transform into females if the dominant female dies

What does sex determination look like in asparagus?

M locus including two genes that are not 100% linked:

• M/m → male (suppresses female development)

• m/m → female

What is haplodiploidy?

Sex determined by the fertilization of the egg, produces sexes with different ploidy

• Unfertilized egg → haploid male

• Fertilized egg → diploid female

What organisms show haplodiploidy?

Hymenoptera → bees, wasps, ants

How is haplodiploidy seen in honeybees?

• Worker bees - female, diploid, infertile

• Drone bees - male, haploid, fertile

• Queen bee - female, diploid, fertile

How have X and Y evolved over time?

• Identical millions of years ago

• Now most organisms have much smaller Y chromosomes that have lost most of its genes

If Y chromosomes have lost most of their genes, how are X and Y chromosomes still in a homologous pair?

The caps of the chromosomes are pseudoautosomal regions that are homologous

How sex determination and development occur in human embryos?

Transcription factors (TFs) drive the development of uncommitted gonads into sexual organs (ovaries/testis)

• TFs from SRY (sex-determining region of Y chromosome) drive development of testis

• Lack of SRY/Y chromosome leads to development of ovaries

What hormones and meiotic processes are seen in the sex-specific human organs?

• Female ovaries → produce estrogen, oogenesis

• Male testis → produce testosterone, spermatogenesis

How do sex hormones enter cells?

Transported through the blood to target cells with specific receptors

How do sex hormones drive sexual differentiation?

Sex hormones activate transcription factors which activate target genes that encode sex-specific traits

How does crossing over differ in mitosis and meiosis in mammals?

• Mitosis → crossing over occurs anywhere in autosomes

• Meiosis → crossing over only occurs in the small pseudoautosomal regions (located on the caps of the chromosomes)

  • Recombination outside these regions results in sex-related abnormalities

Is sex differentiation only seen in animals?

No, found in plants as well

• Papayas show female, male, male with fruit, hermaphrodites

How does sex determination differ across different animal groups?

Sex can be determined by X/Y genes, Z/W genes, or a combination of these genes with ESD

What are Z and W chromosomes?

Sex determining chromosomes found in birds, butterflies and reptiles

• ZW → female (W is similar to the human Y chromosome)

• ZZ → male

How is sex determination seen in cardinals?

• ZW → female, yellow feathers

• ZZ → male, red feathers

How is sex determination seen in bearded dragons?

Sex determined by both ZW genes and environment (temperature)

• ZZ, <32^oC → male

• ZZ, 32-35^oC → mixed

• ZZ, 36^oC → female

• ZW → female, regardless of temperature

What is dosage compensation?

A solution to the issue of females having twice as many X-linked genes that equalizes the amount of protein produced by X-linked genes and autosomal genes

What are 3 different dosage compensation solutions seen in different organisms?

1. Increase activity of genes on male X chromosomes

2. Shut down one X chromosome in females

3. Do nothing (fish, butterflies, birds)

What dosage compensation solution is seen in fruit flies (Drosophila)?

Transcription rates are doubled in male X-chromosomes

What dosage compensation solution is seen in mammals?

One X chromosome is randomly shut down in XX individuals

What is a Barr body?

A highly condensed, inactive X chromosome

• Formed by chromosome inactivation in dosage compensation

• Mammalian cells lacking a Barr body are XY

What is the Lyon hypothesis?

Each cell randomly inactivates one of the X chromosomes

What is the Xist gene?

The gene located on the X chromosome that creates Barr bodies

• Expressed on one X chromosome that becomes the Barr body

• Repressed on the other chromosome that remains expressed

How does the Xist gene create a Barr body?

Encodes a 17000bp RNA molecule that coats the X chromosome the condenses in by recruiting chromatin remodelling proteins

What in Klinefelter syndrome?

Human disease seen in individuals with an XXY genotype

What is Turner syndrome? How does it occur?

Human disease seen in individuals with an X0 genotype

• An XY zygote splits into twins where one loses its Y chromosome

What are sex-linked genes vs X-linked genes?

Sex-linked gene - gene on a sex chromosome

X-linked chromosome - gene on the X chromosome

Are all genes on the X chromosome involved in sex determination?

No, most of them are not

What is an example of a gene on the X chromosome not involved in sex determination?

F9 - blood blotting factor IX

• Deficiency → hemophilia

What nomenclature is used for genes on X chromosome?

Females are homozygous or heterozygous:

• A/A or X^AX^A

• A/a or X^AX^a

• a/a or X^aX^a

Males are hemizygous (half the number of alleles):

• A/Y or X^AY

• a/Y or X^aY

What does a Punnett square look like for an X^A/ X^a female crossed with X^A/Y male

What type of gene is the one responsible for red-green colour blindness?

Recessive X-linked gene

• X⁺ → dominant wildtype (colour vision)

• X^c → colour blindness

What type of gene is the one responsible for coat colour in cats?

Codominant X-linked gene

What type of gene is the one responsible for white patches in cat coats?

Dominant autosomal gene

What genes encode the fur pattern in calico cats?

• X-linked codominant genes encoding orange and black fur

• Dominant autosomal gene encoding white patches

What type of gene is the one responsible for pigeon colouration?

Z-linked gene with multiple alleles showing a complete dominance hierarchy:

• Z^A (ash-red) > Z^B (blue) > Z^b (brown)

• W alleles carry no colour genes

What does it mean that some traits are sex-influenced?

Phenotypes differ between males and females but are due to sex hormones and autosomal genes

What are model organisms?

Organisms used by scientists to study biological processes

• Eg. mice, E. coli, Drosophila

What are some characteristics of good model organisms?

• Short generation time

• Lots of offspring

• Can control mating

• Pure-breeding strains

What do the symbols of a pedigree mean/How do we identify individuals in a pedigree?

What do the lines of a pedigree symbolize/How do we determine relationships in a pedigree?

Note that double lines in a relationship line so inbreeding/consanguinity

What are some different pedigree conventions used to symbolize an individual is an asymptomatic carrier?

What are some numerical conventions seen in pedigrees?

• Roman numerals (I, II, III, etc.) identify different generations in a pedigree

• Arabic numerals (1, 2, 3, etc.) identify family members within a generation

• Siblings are listed left to right in birth order

How are twins symbolized on a pedigree?

With a branched line of descent

What are the patterns of inheritance we can determine through pedigrees?

1. Autosomal recessive

2. Autosomal dominant

3. X-linked recessive

4. X-linked dominant

5. Mitochondrial

What patterns are seen in a pedigree of an autosomal recessive gene?

• Both males and females can be affected

• Affected individuals tend to skip generations

• More likely to appear in the progeny of related parents (inbreeding)

What is phenylketonuria (PKU)?

Human disease that leads to neurological issues caused by a recessive autosomal gene (PAH ^-)

How many people are affected by phenylketonuria (PKU)?

How does the PAH ^- gene cause phenylketonuria (PKU)?

PAH encodes phenylalanine hydrolase protein which converts phenylalanine into tyrosine

• Without it, phenylalanine converts into phenylpyruvic acid that builds up (toxic molecule that damages the CNS)

How is phenylketonuria (PKU) diagnosed and treated?

• Diagnosed through newborn blood tests

• Treated with low phenylalanine diet → less phenylpyruvic acid build up = normal neurological development

What patterns are seen in a pedigree of an autosomal dominant gene?

• Affects both males and females

• Trait does not skip generations

• Unaffected people cannot pass on trait, affected people have at least one affected parent

What is polydactyly in cats?

Condition where cats have extra toes caused by an autosomal dominant allele on the ZRS gene

With X-linked recessive traits, what genotypes produce affected individuals?

• X^a/Y → affected male

• X^a/X^a → affected female

What patterns are seen in a pedigree of an X-linked recessive gene?

• Males are more often affected then females

• Condition often skips generations

  • Affected male → unaffected female → affected male

What are the statistics of the progeny of a female carrier of an X-linked recessive condition?

• 50% of sons are affected

• 50% of daughters are carriers

What is hemophilia A?

Bleeding disorder where blood does not clot properly caused by a recessive X-linked gene

• Common in Queen Victoria’s descendants

What causes hemophilia?

Defect (dysfunctional protein or insufficient expression) in F8 gene (Xq28) that encodes coagulation factor 8

Why is inbreeding bad?

Increased likelihood for recessive traits to be passed on to affected children, many abnormalities in children

• Loss of heterozygotes

With X-linked dominant traits, what genotypes produce affected individuals?

• X^A/Y → affected male

• X^A/X^A → affected female

• X^A/X^a → affected female

What patterns are seen in a pedigree of an X-linked dominant gene?

• Affects both males and females

• Traits do not skip generations

• Affected males pass trait to all daughters and no sons, affected heterogynous females pass to half their sons and daughters

What is fragile X syndrome?

Neurodevelopmental disorder caused by the FMR-1 gene

• Affected males have IQ < 50

• IQ of affected females depends on patterns of X inactivation

  • FRM-1^- is dominant, more FMR-1^- cells = lower IQ

How does the FMR-1 gene cause Fragile X syndrome?

• FMR-1 encodes the FMRP protein which controls proper neuron development and develops connections between neurons

• Strand slippage → sequence repeats

  • >200 repeats silences FMR-1 which leads to atypical neuron connections

What patterns are seen in a pedigree of an mitochondrial gene?

• Traits can only be passed down by the mother

  • Affected mother = all offspring affected

  • Unaffected mother = no offspring affected

Why are mitochondrial traits only passed down by the mother?

• Egg cells contain 200,000 mitochondria

• Sperm cells contain 5 mitochondria which are often lost

What is genetic counselling?

Guidance and counselling provided on genetic conditions, involves:

• Risks of developing a condition

• Family histories of disease

• Probability of a child inheriting a condition

• Prenatal testing for conditions

What is the Hardy-Weinberg equilibrium?

Simple formula to that uses the multiplication rule to calculate/estimate allele and genotypes frequencies for autosomal loci with two alleles:

• Allele frequency: p + q = 1

• Genotype frequency: p² +2pq +q² = 1

What are the 5 assumptions of a population of the Hardy-Weinberg equilibrium?

1. No selection

2. No mutations

3. No migration

4. Large population

5. Random mating

How do you calculate the frequency of an allele?

alle frequency = # of copies of allele / total # of alleles at the locus

• Note that these numbers are relative to the population

What is the general trend seen in allele and genotype frequencies?

• When the frequency of one allele is high, most of the individuals are homozygotes

• Heterozygote frequency is greatest when allelic frequencies are equal (p = q = 0.5)

How is disease risk assessed?

Using:

1. The probability a parent has an affected allele

2. The probability the parent passes on the affected allele

• Questions likely to have partial pedigrees with partial genotype information about the parents

What do Hardy-Weinberg equilibrium calculations with 3 allels on a locus?

• Allele frequency: p + q + r = 1

• Genotype frequency: p² +q² +r² +2pq + 2pr + 2qr = 1

How is inbreeding mesaured?

Inbreeding coefficient (F) - probability that two alleles are identical by descent

• F = 0 → random mating

• F = 1 → all alleles in an individual are identical by descent (seen in image)

What inbreeding coefficients (F) do different degrees of inbreeding produce?

• Self-fertilization (plants) → F = 1 (completely homozygous population)

• Mating between siblings → F = 0.25

  • Mating between first cousins → F = 0.0625

What is quantitative genetics?

The study of quantitative or continuous characteristics, often due to the involvement of several genes

What are qualitative vs quantitative traits?

Qualitative traits - traits with 2 or more discontinuous phenotypes (Eg. coat colour)

Quantitative traits - traits that exhibit a continuous range of phenotypes (Eg. height)

Why is there greater variation around continuous traits?

1. Polygenic regulation

2. Environmental effects

What are polygenic traits?

Multiple genes affect the phenotype of a trait

• More loci → more possible genotypes → more possible phenotypes

Is human height a polygenic trait?

Yes, over 12000 single-nucleotide polymorphisms (SNPs) are associated with human height

• Eg. a subset of genes expressed in bone growth plates associated with height differences

What are some examples of environmental effects on phenotype?

• Season

• Light

• Nutrition

What is phenotypic plasticity?

The ability of a genotype to express different phenotypes under different environmental conditions

• All genotypes respond in a similar way

What three components can phenotypic variance be broken down into?

1. Genotype (V_genetic)

2. Environmental effects (V_{environmental})

3. Interactions of genotype and environmental interactions (V_GxE)

• V_{phenotype =} V_{genetic +} V_{environmental +} V_GxE

How do genotypes and environmental effect interactions affect pehnotype?

Genotypes behave differently in different environments

• Eg. wet environment → aa taller; dry environment → AA taller

How does PTC tasting demonstrate population genetics?

Phenylthiocarbamide (PTC) is responsible for the bitter taste in foods like beer and brussels sprouts

• One gene determines if you are taster or non-taster of PTC, and phenotypes follow Mendelian ratios (3:1 taster:non-taster)

What are complementary genes?

Two genes are both required to produce a wild phenotype

• Eg. petal colour in harebells

What Mendelian ratios are seen in traits with complementary genes?

9:7

• In the example photo (harebell petal colour), w1 and w2 are complementary genes where w1⁺ and w2⁺ are completely dominant to w1^- and w2^-

What are some possible biochemical pathways for complementary gene action?

1. The complementary genes encode for two different enzymes

2. The complementary genes encode for two subunits of one enzyme

What are duplicate genes?

Sometimes genes have redundant functions and only one of two genes is needed to produce the phenotype

• Eg. seed coat colour in wheat

What Mendelian ratios are seen in traits with duplicate genes?

15:1

• A dominant genotype at either locus deermines phenotype

What is epistasis?

One gene masks or interferes with the expression of another gene

What are the two types of epistasis?

1. Recessive epistasis

2. Dominant epistasis

What is recessive epistasis?

When the recessive phenotype of one gene conceals the phenotype of a second gene