Genetics Exam 1 Study Guide

Monohybrid Cross

proved theory of blended inheritance wrong

P_o = True Breeding Dominant & Recessive (Homozygous)

F₁ = Heterozygotes

F₂ = 3:1 Dominant Recessive Phenotypic Ratio

Reciprocal Cross

proves equal parental contribution to progeny

2 crosses with 2 same phenotypes, but each cross has a different sex holding each phenotype

Ex:

• Cross 1: male dominant trait & female recessive trait

• Cross 2: female dominant trait & male recessive trait

• Same F1 & F2 outcomes = equal contribution

Gregor Mendel

Father of Genetics

Conclusions:

• male & female parents contribute equally to progeny (reciprocal cross)

• inheritance is not blended (monohybrid cross)

Theories:

• dominant & recessive traits

• Theory of Particulate Inheritance

  • traits are determined by discrete units that are inherited intact through generations (genes!!)

  • each individual has 2 particles (alleles) in genotype, but they pass only 1 on to progeny

Mendel’s First Law

Principle of Segregation

during gamete formation, members of a pair of alleles segregate into separate gametes (Tt → T + t) (gametes are haploid)

these gametes form in equal frequencies

Homologous Chromosomes

every gene resides on a chromosome, every individual has 2 copies of every chromosome (homologs)

autosomal: same structure, size, and genetic loci - differ in variation of gene (allele)

sex: x + y chromosomes or x + x (not same size or structure, but code for same gene - can be different alleles)

Test Cross

1) determines unknown genotype of dominant phenotype; cross unknown genotype with heterozygous recessive individual

• homozygous dominant genotype = 100% dominant phenotypes in progeny

• heterozygous genotype = 50% dominant & 50% recessive phenotypes in progeny

2) cross individual with known genotype (F1) with homozygous recessive to determine if its gametes show deviation from independent assortment

• unlinked genes (independent assortment) → 1:1:1:1 phenotypic ratio (1:1 parental to recombinant gene)

• any deviation from ratio above indicates linkage

Chromosome

double stranded DNA molecule containing genetic information arranged in a linear sequence

most of the cell cycle, DNA is in a dispersed state in nucleus (chromatin)

distinguished by: size, location of centromere in relation to telomeres, and genes present

Eukaryotic Chromosome Components

linear

unique shape & size

centromere: constricted region that provides binding site for proteins during mitosis & meiosis

telomeres: on ends of chromosomes

centromeres & telomeres have no genes, but have highly repetitive DNA

Chromosome Names Based on Centromere Location Relative to Telomeres

Metacentric: centered centromere

• no p/q arms

Sub-Metacentric: centromere is slightly closer to one telomere

• p arm (top) is slightly shorter than q arm (bottom)

Acrocentric: centromere is even closer to one telomere

• p arm (top) is significantly shorter than q arm (bottom)

Telocentric: centromere is essentially all the way at one end

• p arm is essentially nonexistent

Ploidy

Number of sets of chromosomes

N = # of distinct chromosomes

humans: 2n = 46 chromosomes

gametes: n = 23 chromosomes

Mitosis vs Meiosis

Mitosis

• 1 cell division

• product is 2 identical diploid cells

• somatic cell formation

Meiosis

• 2 cell divisions

• product is 4 non-identical haploid cells

• gamete formation

Cell Cycle

stages 1 cell goes through as it grows & divides

G_o → non-dividing phase; cell is in stable state at constant size

Interphase:

• G₁ → 1st gap/”growth” phase; prep phase; proteins needed for cell division are made

• S → DNA synthesis; chromosomes are duplicated (sister chromatids)

• G₂ → 2nd gap/”growth” phase; any damaged DNA must be repaired

M → mitosis phase; cell division

How to count chromosomes/chromatids

count centromeres for chromosomes

count telomeres on one end for chromatids

Mitosis Sequence

Prophase

• chromosomes condense

• mitotic spindles form outside nucleus

• nuclear envelope breaks down

Metaphase

• microtubules from spindle pole attach to each chromosome at centromere

Anaphase

• proteins holding sister chromatid centromeres together are degraded

• sister chromatids separate (disjoin) & move to opposite spindle poles

• # of chromosomes double! (# of chromatids stay the same)

Telophase

• nuclear envelope reforms around each daughter cell

• chromosomes uncoil

• spindle disappears

• cytokinesis: cytoplasmic division

Meiosis Sequence

Prophase I

• chromosomes condense, spindles form, nuclear envelope breaks down

• homologous chromosomes pair (synapse)

• crossing over may happen (recombination)

  • 1 sister chromatid from each homolog participates in a single cross-over event

• continuous process of 5 stages

  • leptotene: condensation begins

  • zygotene: synapsis begins

  • pachytene: condensation continues & recombination

  • diplotene: synapsis breaks down & chiasmata keep homologs joined

  • diakinesis: moving apart

Metaphase I

• each pair of homologs takes up a position on metaphase plate

• independent assortment: orientation of each pair of homologs with respect to all others is random

Anaphase I

• homologous pairs disjoin & move to opposite poles

• principle of segregation: separation of particles to create gametes with 1 particle

Telophase I

• nuclear envelope reforms

• interkinesis occurs (cytokinesis between meiosis I & II)

• 2 haploid cells form

• total number of chromosomes in each cell is half of starting number

Prophase II

• chromosomes condense, spindles form, nuclear envelope breaks down

Metaphase II

• sister chromatids position themselves on metaphase plate

• looks like mitotic metaphase, but each cell has half as many chromosomes

Anaphase II

• sister chromatids disjoin & move to opposite poles

• chromosome # in celll has now doubled

Telophase II

• nuclear envelope reforms

• cytokinesis

• 4 unique haploid gametes

Mendel’s 2nd Law

Principle of Independent Assortment

viewed in metaphase IThe

orientation of each pair of homologs is independent of orientation of other pairs

Dihybrid Cross

can observe inheritance of two traits

P_o → true breeding

F₁ → heterozygotes

F₂ → 9:3:3:1 phenotypic ratio

Probability Rules

Multiplication Rule:

• “and”

• probability that 2 independent events happen simultaneously or in a particular order

• independent = outcome of one has no influence on outcomes of other

• multiply probabilities

Addition Rule:

• “or”

• probability that either 1 or 2 mutually exclusive events happen

• sum of independent probabilities

• mutually exclusive: cannot happen at same time

• if not mutually exclusive: sum of independent probabilities - p(both events occur)

Binomial Expansion Equation

calculates probability of several events when they can happen in any order

X² Test

compares observed values (experimental results) with expected values (calculated based on given info)

allows us to evaluate null hypothesis: difference between observed & expected is due to chance

determines p-value → probability difference is due to chance

• p < 0.05 → reject null hypothesis ; difference is due to something other than chance

Selecting mode of inheritance of a trait in humans using pedigree

use “best guess” which makes the fewest amount of assumptions for individual genotypes

Pedigree Symbols

Tricks to Figuring Out Pedigree Diagrams & Mode of Inheritance

if trait is dominant & completely penetrant, each affected child has an affected parent

if trait is autosomal, both sexes are equally affected

if trait is sex linked, on sex is affected more than others (if females are affected it is never Y-linked)

• x-linked - affected fathers have 100% affected daughters

assumptions:

• never assume individuals marrying into family are carriers!

• MOST affected individuals are het (does not count as an assumption)

Sex Influences on Heredity

Genetic Maternal Effect

• genotype of progeny is inherited from mom and dad, but phenotype is always determined by genotype of mom

• often due to egg providing cytoplasm to zygote, which has proteins synthesized by mom, so progeny starts off using mom’s machinery/proteins

Cytoplasmic Inheritance

• chloroplasts & mitochondria are cytoplasmic organelles that contain genetic material

• during cell division, mitochondria randomly segregate into progeny cells

• in 1 cell, different mitochondria could have distinct mutations that affect overall phenotype (each cell can have diff # of mutant mitochondria)

• if there is only mutant DNA in mitochondria, there is expression of mutant gene

• from mother because egg provides cytoplasm

• can be the reason disease shows later in life because as cells divide, there is more of a chance that a mitochondria with fully mutant DNA occurs

• traits are expressed in both males and females

• reciprocal crosses give different resulst

Genomic Imprinting

• gene expression affected by whether gene comes from mom or dad

• allele from one parent is silenced while the other is expressed

• due to chemical modifications on chromosome that cause a chromosome to be too tightly packed to expressed

Dominance Relationships

Complete Dominance: phenotype of heterozygote looks like phenotype of homozygote (mendelian)

Incomplete/Partial Dominance: phenotype of heterozygote is an intermediate between phenotypes of different homozygotes (non-mendelian)

Codominance: heterozygote has phenotypes of both homozygotes

in partial/codominance, do not use big letter, little letter because that assumes complete dominance

Allelic Series

any gene has multiple forms/alleles within population, but each individual member can only carry 2 alleles

alleles may form a dominance series, which can result in deviation from mendelian ratios

Lethal Alleles

found in essential genes

can be recessive or dominant

crossing 2 heterozygotes gives 2:1 phenotypic ratio

Pleiotropic Gene

single gene influences multiple phenotypes

Penetrance

proportion of individuals with a particular genotype that display expected phenotype

incomplete penetrance: less than 100% of individuals with a given genotype show expected phenotype

• may give a trait an appearance of skipping generations

• can allow lethal alleles to persist in populations

• due to varying genetic backgrounds and environmental effects

Variable Expressivitiy

phenotype varies among organisms with identical genotypes

variation in severity of trait

due to varying genetic backgrounds and environmental effects

Environmental Modification

environmental conditions can affect phenotype

Gene Interaction

genes at 2 or more loci (non-allelic) influence same trait

can lead to:

• novel phenotype

• epistasis

• complementation

Epistasis

allele(s) at one locus mask effect of genotype at 2nd locus

one of the outcomes of gene interaction

Complementation

crossing 2 recessive mutants generates wild-type progeny (proves mutant genes are non-allelic - diff genes)

one of the outcomes of gene interaction

Complementation Test

cross 2 mutant strains together & look for complementation (wild-type phenotype) in progeny, meaning the two strains are found on two different genes

mutant strains must be recessive

view F1 progeny for wild-type phenotype

Sex-Linkage

sex chromosomes are heteromorphic (diff shapes), but still act homologous during meiosis

they have pseudoautosomal regions that allow chromosomes to pair during prophase (this is where genetic recombination between X & Y occur)

(autosomes = homomorphic)

reciprocal corsses give different results

Sex Determination (humans, other animals, and fruit flies)

Humans → XX/XY System

• presence of Y chromosome (which has the SRY gene found close to telomere of p arm) confers maleness

• males = heterogametic (XY)

• females = homogametic (XX)

Birds, Butterflies, Fish, some Reptiles → ZZ/ZW System

• females = heterogametic (ZW)

• males = homogametic (ZZ)

Fruit Flies → ratio of # of X chromosomes : # of sets of autosomes

• 1 → female

• 0.5 → male

• <0.5 → metamale

• >1 → metafemale

• between 0.5 & 1 = intersex

• 0.5 & missing Y → sterile male

  • Y chromosome is necessary for proper sperm development or morphology (Y is required for male fertility, but not sex determination)

Nondisjunction

creates gametes with incorrect # of sets

either an incomplete set or more than one complete set (ex: XO or XXY)

Dosage Compensation

corrects potential imbalance in amount of X-linked gene products present in cells of males vs females

necessary because unequal number of sex chromosomes in males and females

done via x-inactivation

• is random (randomly chooses x chromosome to inactivate, can be from mom or dad)

  • 50/50 split between inactive x genes in mom and dad

• happens early in development

• barr body forms

• leads to mosaicism in females

  • in human females, ~50% of cells in body should have each X chromosome inactivated (50 recessive & 50 dominant) → het for recessive x-linked trait has enough cells expressing “normal” X in every tissue to allow normal phenotype to be expressed

  • but if x-inactivation is not random, mild phenotypes may be observed

• barr bodies passed on through mitosis

Sex-Influence Traits

traits which are more common in 1 sex

genes are autosomal

sex affects whether allele is dominant or recessive

Sex-Limited

extreme example of sex-influenced traits

genes are autosomal

allele has 0 penetrance in 1 sex

traits are often related to 2˚ sex characteristics

Gene Linkage

observed as a deviation from independent assortment toward parental genes

linked genes are on the same chromosome, so they move together during gamete formation

2 Ways to Represent Linkage

Physical Linkage (# base pairs between) - physical proximity of genes on a chromosome; more precise method

Statistical Linkage (map units/centiMorgans) - how we observe physical linkage based on experimental data

Complete Linkage

genes are so close together that they never assort independently

100% parental gametes, no recombinant gametes

Allelic Configurations

cis/coupling → each chromosome has only dominant or recessive alleles

trans/repulsion → each chromosome has 1 dominant and 1 recessive allele

Linkage Nomenclature

Independent Assortment Parental & Recombinant Gene Ratio

50% parental to 50% recombinant

unlinked genes

Incomplete Linkage

more parental gametes than recombinant gametes (but recombinant genes are present)

Crossing Over

physical exchange of chromosomal material between homologous chromosomes

results in recombination between genes on homologous chromosomes at 2 different loci

more crossing events between genes that are farther apart

RF equation

f(recombination) = RF = # recombinant gametes/total gametes

RF represents the frequency of recombination between genes during prophase I

RF is never greater than 50%!

1% RF = 1 map unit = 1 centimorgan

Triple Test Cross

looks at recombination among 3 genes

2 types of single crossover events are possible

• terminal alleles differ

double crossover event (RARE) can happen if both single crossovers happen

• middle alleles differ

Coefficient of Coincidence (coc)

how often a double crossover event actually happens when it is expected

coc = observed double crossover events / expected double crossover events

expected double crossover events = p ( one single crossover event occurs AND the other single crossover event occurs) x # of total gametes

• # of single crossover events include the times it happens in double crossover (ex: 4 single crossover events & 2 double crossover → single crossover occurred 6 times)

Interference

how often double crossover event is inhibited (doesnt happen when it should happen)

I = 1 - coc

ABO Blood Type

Shows dominance (I^A > i, I^B > i) & codominance (I^A = I^B, heterozygotes has phenotypes of both homozygotes)

I^AI^A or I^Ai = type A

I^BI^B or I^Bi = type B

I^AI^B = type AB

ii = type O