BIOC15: Genetics Midterm

Genetics

Genetics

Study of genes and heredity, including the inheritance of traits from one generation to the next. Biological function of genes. Investigates genetic code and its role in determining an organism’s characteristics. Genetic variation, mutations, and their impact on an organism’s development and functioning.

DNA

Hereditary material composed of four nucleotides (A, C, T, G) that encodes all information from an organism.

Genes

Segments of DNA transcribed to RNA to produce proteins or functional RNA molecules.

Mendelian Genetics

Principles of inheritance established by Gregor Mendel, still applicable today.

Beadle and Tatum

‘One gene, one enzyme hypothesis’. Each gene encodes a single enzyme. Incomplete picture. A linear reaction of DNA to RNA to Protein

Alleles

Two versions of the same gene that differ in DNA sequence and/or function.

Polymorphic

Gene has multiple wild-type alleles. Multi-allelic.

Hemizygous

Individual has one copy of a gene. Instead of homozygous or heterozygous. Common in males on Y-linked traits, they only have one Y chromosome.

Linked SNPs (single nucleotide polymorphism)

Outside of gene. No effect on protein production or function.

Causative SNPs (single nucleotide polymorphism)

In gene. Non-coding: changes amount of protein produced. Coding: changes amino acid sequence.

Pleiotropy

A single gene can encode for several enzymes with different functions, affecting multiple phenotypes.

Mendel

Artificial selection was the first applied genetic technique. Purposeful control of mating by choice of parents for the next generation. Domestication of plants and animals was a key transition in human civilization. Important crops, for example, rice, wheat, corn, and herds of pigs, sheep, and cattle are the results of selective breeding over many generations.

Mendelian process

prevent selfing (removed stamen) → observed discrete traits → pure-breeding (true breeding lines, inbred) → reciprocal crosses (reversed whether trait was coming from male or female to see egg and sperm importance).

1800s

Documented hereditary. DNA first identified.

1900s

Theory of heredity. Chromosome (fly room). X-ray induce mutations. Nuclei stores genetic information. One gene, one endzyme hypothesis. Genetic recombination in corn. A-, C-G. Double helix dtructur. mRNA. Sequencing began.

Mendelian genetics themes

1. Variation is widespread in nature and provides for continuously evolving diversity

2. Observable variation is essential for following genes from one generation to another

3. Variation is inherited by genetic laws, which can explain why like begets like and unlike

4. Mendel’s laws apply to all sexually reproducing organisms

Pangenesis

If you mix different things, you get a mix of the two. Blending inheritance. Why Darwin was struggling.

Male-dominated inheritance

An issue with understanding inheritance in Darwin and Mendel’s theories. if the mother has the trait, all her sons will have it.

Experiments in plant hybrids

By Gregor Mendel, 1866. Became a cornerstone of modern genetics. Wasn’t discovered until 1900s.

Pea plant traits

• Colour of peas (yellow or green)

• Colour of pod (yellow or green)

• Colour of flowers (purple or white)

• Shape of peas (round or wrinkled)

• Shape of pods (smooth or indented)

• Position of flowers (along stem or at tip)

• Plant height (tall or dwarfed)

Product rule

Probability of two independent events occurring together in the product of their individual probabilities. P(1 and 2) = P1 X P2

Sum rule

Probability of either of two mutually exclusive events occuring is the sum of their individual probabilities. P(1 or 2) = P1 + P2

Test cross

Cross individuals with dominant phenotype to a true breeding recessive individual (yy) and score progeny. If you cross with a recessive phenotype, it can give yy, while dominant phenotype could give Yy or YY.

Monohybrid Cross

A genetic cross between individuals that differ in one trait, typically resulting in a 3:1 phenotypic ratio. 1:2:1 genotypic ratio. Two different alleles of a single gene.

Dihybrid Cross

A genetic cross between individuals that differ in two traits, typically resulting in a 9:3:3:1 phenotypic ratio.

Law of Segregation

Alleles of the same gene segregate during gametogenesis with equal probability.

Law of Independent Assortment

Pairs of alleles segregate independently of each other during gamete formation, results in parental and recombinant genotypes in the offspring. Proven with dihybrid cross.

Testcross

A cross between an individual with a dominant phenotype and a homozygous recessive individual to determine the genotype of the dominant individual.

number of gametes calculation

2ⁿ = number of different gametes. n = number of heterozygotes. Aa Bb Cc DD = 2³ = 8 kinds of gametes.

Branched line diagram

Predict proportion of progeny from multi-hybrid crosses

Pedigree

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.

Vertical pattern of transmission

A trait that appears in an affected individual, and in at least one parent, one of the affected parent’s parents, and so on. With a rare trait, it shows that disease-causing allele is dominant. Huntingtons.

Horizontal pattern of transmission

A trait that appears in an affected individual may not appear in any ancestors, but it may appear in some of the siblings. A pedigree with this usually indicates a rare recessive disease-causing allele. Affected individuals are often products of consanguineous mating. Cystic fibrosis.

Complete dominance

Hybrid resembles one of the parents

Incomplete dominance

Phenotype ratio reflects the genotype ratio. A dominant allele doesn’t necessarily make something as it is, it’s more of an inbetween.

Codominance

Both phenotypes show up equally in the heterozygote. Often occurs because both alleles code for a functional protein. Phenotype reflects genotype ratio again. Spot and/or dot example

Ciliary Dyskinesia

Genes that encode proteins necessary for the function of cilia and flagella. A Non-functional recessive allele results in respiratory issues and sterility.

Frizzle chickens

A mutation on the a-Keratin (KRT75) gene. Effects feather shape and egg laying ability. They wanted the get these cool feathers and bred for them, but there were side effects.

Incomplete dominance of two genes

White all the way to deep purple. All these different gene combinations affect the phenotype. Not mutually exclusive extensions to Mendel’s laws. You can have multiple things going on. This is kinda like something like heigh I imagine.

Epistasis

Interaction between genes where the effect of one gene masks the effect of another gene.

Recessive epistasis

There will be a functional pathway made. Then dominance and colour are determined further. No functional pathway will produce a separate phenotype. You need to create the pathway, for the other genotypes to even have an effect. Recessive gene does the blocking. Dominant alleles of both genes function in a common pathway to affect a common outcome. Lab colour example.

Dominant epistasis

The recessive allele may allow for colour, but the dominant does not. If the dominant dysfunctional allele of gene B is present, then it does not matter what allele A has. Dominant allele does the blocking. Green squash example.

Redundancy

One or more of the genes affecting a phenotype are superfluous. Occurs when genes function in parallel. Two genes that are redundant to each other, two or more effecting. Still get broad leaf, you just need one of the genes to have a dominant allele. Two genes affect the same phenotype, and having a functional allele of either gene is enough. 15:1 ratio for Aa Bb X Aa Bb.

Locus heterogeneity

Mutations in any of a number of genes give rise to the same phenotype. Flower colour in peas is a heterogenous trait. Flower colour in pears - any recessive mutation results in a white flower.

Reciprocal recessive epistasis.

Like locus heterogeneity. The dominant alleles of two genes acting together (A– B–) produce a characteristic, while the other three genotypic classes (A– bb, aa B–, and aa bb) do not.

Complementation

Recessive mutations in multiple genes have the same phenotype. Dominant phenotypes can originate from two recessive parents, if their recessive mutations were in different genes. Deaf example.

Reciprocal dominant epistasis

Dominant allele of each gene masks the effects of recessive of recessive allele of the other gene. (15:1, redundancy)

Neomorphic alleles

Generates novel characteristics

Antimorphic alleles

Removes a characteristic

Penetrance

Same genotype doesn’t result in same phenotype. Can be complete (genotype = same phenotype) or incomplete (genotype = same phenotype).

Expressivity

Levels or shades of a phenotype. Can be varying or unvarying.

Modifier genes

Have a subtle influence on phenotype. Cause secondary effect that alters the phenotype produced by other genes.

Conditional lethal alleles

Causes death under specific conditions. Permissive conditions (wild-type behaviour), restrictive conditions (causes lethality). Mutant shibirie allele in Drosophila (die at 29^oC)

Phenocopy

A change in phenotype arising from environmental agents that mimics the effects of a mutation in a gene. Not heritable because they do not result from a change in a gene.

Polymorphism

Deals with forms in which the variation is discrete or strongly bimodal/polymodal. Not continuous variation though.

Genetic Map

A representation of the arrangement of genes on a chromosome based on recombination frequencies.

Chromosomal Theory of Inheritance

The theory that genes are located on chromosomes and that chromosomes segregate during meiosis. 1902 by Sutton and Boveri.

Non-lethal genetic disorders

Down’s syndrome (extra 21), Edward’s syndrome (extra 18), Patau’s syndrome (extra 13). The Trisomy.

Sex chromosome genetic disorder

Turner’s (single X), Klinefelter’s (XXY male), Triple X syndrome (XXX female), XYY syndrome (XYY males)

Prophase (Mitosis)

Chromosomes condense and become visible. Centrosomes move apart toward opposite poles. Nucleoli begin to disappear. Microtubules are created.

Prometaphase (Mitosis)

Nuclear envelope breaks down. Microtubules from centrosomes invade the nucleus and connect to kinetochores in the centromere of each chromatid. Mitotic spindle forms from three kinds of microtubules (astral, kinetochore, and polar), first two connect.

Metaphase (Mitosis)

Chromosomes align on the metaphase plate with sister chromatids facing opposite poles. Forces pushing and pulling chromosomes to or from each pole are balanced in equilibrium keeping chromosomes in place. Everything is aligned at center of the cell.

Anaphase (Mitosis)

Centromere of all chromosomes split simultaneously. Connection between centromeres of the sister chromatids is severed. Kinetochore microtubules shorten and pull separated sister chromatids to opposite poles (characteristic V shape)

Telophase (Mitosis)

Nuclear envelope forms around each group. Nucleoli re-form. Spindle fibers disappear. Chromosomes uncoil and reform as a chromatin.

Cytokinesis (Mitosis)

Begins during anaphase, but not completed until after telophase. Cytoplasm of parents cells split into two daughter cells with identical nuclei. Mitosis finishes. Animal cell - contractile ring. Plant cell - cell plate.

Syncytial embryo

Cytokinesis does not always occur after mitosis. In fertilized drosophila eggs, they do 13 rounds of mitosis without cytokinesis. Thousands of nuclei in a single cell.

Meiosis overview

1: Reduces the chromosomes from 2n to n

2: produces four haploid nuclei.

Non-disjunction

Failure of homologous chromosomes to separate properly during meiosis, leading to gametes with abnormal chromosome numbers.

Diplotene

Prophase 1. Synaptonemal complex (protein structure that forms between homologous chromosomes during meiosis) dissolves. A tetrad of four chromatic is visible. Crossovers points as chiasmata holding nonsister chromatids together.

Diakinesis

Prophase 1. Chromatin thicken and shorten. At the end of prophase 1, the nuclear membrane breaks down and the spindle begin to form.

Synaptonemal complex

Forms a zipper between homologous chromosomes, holding them together. When crossing over occurs, points stay there past complex disappearing. Plays role in proper segregation of 4 divided.

Metaphase 1

Tetrads line up along the metaphase plate. Each chromosome of a homologous pair attaches to the fibers from opposite poles. Sister chromatids attach to fibers from the same pole. Law of segregation - equal probability of alleles of different genes sorting.

Anaphase 1

Sister centromeres remain connected to each other. The chiasmata dissolves. Homologous chromosomes move to opposite poles.

Telophase 1 and interkinesis

Similar to interphase, but not chromosomal duplication. The nuclear envelope re-forms. Resultant cells have half the number of chromosomes. Cytokinesis separated daughter cells. Chromosomes decondense (some species).

Prophase 2

Chromosomes condense. Centrioles move towards the poles. The nuclear envelope breaks down at the end.

Metaphase 2

Chromosomes align at the metaphase plates. Sister chromatids attach to spindle fibers from opposite poles.

Anaphase 2

Sister centromers detach from each other, allowing sister chromatids to move to opposite poles.

Telophase 2

Chromosomes begin to uncoil. Nuclear envelopes and nucleoli re-form.

Cytokinesis (meiosis 2)

The cytoplasm divides, forming four new haploid cells.

SRY (sex determining region of Y)

Primary determinant of maleness. Always present in XX males. Always nonfunction in XY. The + version is in males. If you have one it makes you male. SRY is non-functional in XY females and functional in XX males.

Pseudoautosomal regions (PARs)

Human chromosomes contain genes unrelated to sex. Some genes are present on both the X and Y chromosomes of humans, located at the ends of the Y chromosome.

Heterogametic sex

Sex with two different kinds of gametes (XY males in humans, ZW females in birds)

Homogametic sex

Sex with one type of gamete (XX females in humans, ZZ males in birds).

Gametogenesis

Gamete formation. Differs across species. Involves meiosis as well as some specialized events after meiosis. Oogenesis produces on ovum from each primary oocyte. Spermatogenesis produces 4 sperm from each primary spermatocyte.

Spermatogenesis

Four haploid sperm produced by symmetrical meiosis of each spermatocyte. Mitosis and meiosis occur throughout adult life. Entire process takes approximately 48 to 60 days. Billions of sperm produced over lifetime.

Spermatid → sperm

Oogenesis

You have mitosis of germ cells in the fetal ovary. The cells are oogonia. They go to meiosis 1. when they grow it gets nutrients. Oocyte female is very big. Oocytes get arrested during this phase. Only one of the gametes polar bodies or something with all the cytoplasm. One daughter cell gets all nutrients and matures into a gamete. 2 polar bodies. Division of genetic material is the same but 2 are asymetrical polar bodies.

Morgan (1910)

Discovered white-eyed drosophila mutant and did crosses. Eye colour is associated with sex. If he crossed red eye female and white eye male, offspring all has red eye, cuz of red-eye from mother. Only males had white eyes when mother had white eye allele.C

Crisscross inheritance

Daughters inherit the phenotype of their fathers, sons inherit phenotype of their mothers.

X-linked dominant

Affected male → all female progeny will have it. Males will depend on state of mother.

Dosage compensation

Offsets what would be double the gene products in the homogametic versus heterogametic sex.

Sex-limited traits

affect a structure or process found in only one sex. For example Drosophila stuck mutant males can’t separate from female after mating

Sex-influenced traits

Appears in both sexes, but hormonal differences may cause differences. Male pattern baldness.

Gene-linkage discovery

X-linked Drosophila. Two X-linked genes in Drosophila. w+ (red eyes) and w (white eyes). y+ (brown body) and y (yellow body). F1 males get their only X chromosomes from their mothers, F1 females are dihybrids.

Independent assortment

Alleles of genes on different chromosomes always assort independently. Alleles of genes on same chromosomes need recombination to assort independently. Align randomly at plate.

Crossing over

Most likely to happen somewhere along the two homologous chromosomes every meiosis, but it might not happen between two specific genes. Relative to those genes we call.

None: 4 parental

Single: 2 parental, 2 recombinant

Double: varying proportions of parental and recombinant gametes.

Recombinant frequency

A measure of physical distance between two genes

1 RF = 1 map unit (m.u.) = 1 centrimorgan (cM)

0%<RF<50% → linked. Sometimes phenotypes look the same.

Gene mapping

1. Start with known parental genotypes with mutations for two genes

2. Score the progeny for the number of recombinants

3. Divide the number of recombinants over total progeny to get recombination frequency (m.u.) between the two genes.

4. Repeat for another pair of genes

5. Eventually you will get a genetic map

Two point crosses

Crossing two genes to calculate recombinant frequencies (m.u). Issues: time and labour, actual distances between genes do not always add up, if two genes are very close together it is difficult to determine gene order.

Three point crosses

cross individuals with mutations in three genes. Testcross progeny have four sets of reciprocal pairs of genotypes. Most frequent pair has parental configuration of alleles. Least frequent pair results from double crossovers. Examination of double crossover class reveals which gene is in the middle.

Coefficient of coincidence

CC = obs double crossovers / expected double crossovers

Obs = [(x + y) / total] x 100

Exp = RF of (v-ct) / RF of (ct-cv)