Gene4200 2nd exam

Alleles

different variations/forms of genes

Wild Type Alleles

the full function of a gene that gives rise to a “normal phenotype”

Sequence Changes can

impact regulatory regions

Alleles result from

sequence variation

Allelic differences can be used to

understand gene function/regulation

In diploid organisms

each chromosome can harbor a different allele of a given gene

dominant alleles

are always expressed regardless of the other alleles present

Recessive alleles

are expressed only if both the connected alleles are recessive

Incomplete dominance

Heterozygotes  are an intermediate trait between homozygous genotypes

Codominance

Heterozygotes have traits associated with both genotypes (ex. blood type)

Penetrance

percentage of cases in which a particular phenotype is observed when the specific genotype is present

Expressivity

the extent of the phenotype

Penetrance and Expressivity can

be impacted by environment, genetic background, stochasticity, thresholds, timing etc.

Amorphs or “nulls”

complete loss of gene function

Hypomorphs

partial loss of function

Hypermorph

increase in normal gene function or activity

Antimorph

acts in opposition to or interferes with normal gene activity

Neomorph

gain of function that is different from normal function

Complementation test

a type of type test that uses crosses to determine whether two alleles are on the same locus

Rescue experiments

Often done to test for specificity of effect or to confirm the allele is in a particular gene

Allelic differences

can be used to understand gene function/regulation

Two ways to find alleles

1. Natural sequence variation in populations

2. New sequence variation induced by mutagenesis

Radiation

Induces large deletions, duplications, translocations and inversions; Can result in some cool phenotypes like Position effect variegation

Chemical mutagens

Cause changes to the DNA sequence; Often point mutations :transitions and/or transversions

Transitions

between similar ring structure

Transversions

between different ring structures

EMS

Alkylating agent that induces GC to AT transition mutations

Insertional mutagenesis

Transposons that are capable of integrating randomly across genomes; different effects depending on location of insertion

Germline transmission of mutations

critical for recovery

Mutation rate

number of total mutations in a given germ cell

Forward genetics

given a phenotype and figure out what gene causes it

Reverse Genetics

given a gene and figure out when given a mutation is the phenotype

Genetic Screens 1st Step

Form a biological question

Genetic Screens 2nd Step

Get a mutant population

Genetic Screens 3rd Step

screen for phenotype

Genetic Screens 4th Step

Filter mutants

Genetic Screens 5th Step

Identify site of mutation

Traits to choose a phenotypic readout

Morphological phenotypes, survival, specific cellular phenotypes, behavior

Saturated Screen

when you’ve hit all genes involved in a particular phenotype at least once

Recombination

exchanges material between chromosomes and genes are less likely to combine when they are close. IF a gene fails to recombine with your marker then that means your marker is nearby the gene

Haplotype

a group of alleles/sequence variants that are

inherited together from a single parent. These may also be

referred to as linked alleles/variants

Polymorphism

place in the genome where there is a sequence variant between two genetic backgrounds

SNP

Single Nucleotide Polymorphism A/T

SSLP

Simple Sequence length Polymorphism. AAAAAAA/AA

For recessive mutations

you would need mutagenized background on both alleles

Whole genome sequencing

Allows us to not have to look for markers one by one

Pedigree

A chart that diagrams the inheritance of a

trait or condition through generations of a family

How do we find the variants(s) responsible for a given disease

1. Sequence affected individual’s genome

2. Compare sequence of affected individual’s genome

to human reference sequence/ unaffected individuals

3. Look for differences

Filtering Mutations

1. Focus on genes

2. Exclude benign variants

3. Especially look for variants that are likely to have a big impact on the protein

Inheritance models can inform

recessive model

Sporadic mutation

no inheritance; unlikely to impact multiple sibling

Exome Sequecing

sequencing just the exons, could miss something but unlikely

Qualitative Traits

phenotypes with discrete and easy to measure values; eg. color

Quantitative Traits

individuals that cannot be classified into discrete values; eg height

Threshold Traits

an underlying quantative basis that determines where you have the trait or not in a discrete trait

How many phenotypic classes for n loci

2n + 1 for number of classes

Quantitative trait loci (QTLs)

contribute to quantitative trait variation; Could be many all contributing small effects or a few with large effects; region contributing to where a phenotype is

QTL mapping

Perform a cross, generating and scoring many F2;

Choose parents that differ in phenotype and for many

markers (markers must be heterozygous in F1!)