Genetic Variation- Chromosomes, Sequence, and Variation Flashcards
Genetics
relating traits we care about to variation in the genome
Majority of genome is
not protein-encoding; minuscule amount of genome codes for protein compared to rest of genome
Alleles
sequence variation at a site in the genome; mammalian genes both have maternal and paternal allele
single nucleotide polymorphisms
SNPs; these are type of genetic variability located throughout genome; single base pair difference in sequence of different chromosomes in population 1/200 bp on average; discovered by sequence alignment
heterozygous for SNP
overlap of A and T at same position; chromatogram intensity often 1/2 height (bc only have templates have A or T nucleotide); paternal and maternal inherited chromosomes are different
human genome size and autosome #
3.2Gb, 22 autosomes
mouse genome size and autosome #
2.6Gb, 19 autosomes
Dog genome size and autosome #
2.41Gb and 38 autosomes
Horse genome size and autosome #
2.7Gb, 31 autosomes
chimp genome size and autosome #
3.3Gb, 22 autosomes
cat genome size and autosome #
2.7 Gb, 18 autosomes
cow genome size and autosome #
2.87Gb, 29 autosomes
Why are sequence variations pervasive in genome
genome is encoded in physical molecules so it is subject to damage from chemically reactive species, repair failures, and copying mistakes; elements in genome are capable of self replication -> sequence changes
transposable elements
active elements within the genome that are capable of self-replication -> sequence changes to the genome
Variation in genome effect
genes must have correct sequence for proper function; some changes dnt impact fx others reduce or destroy ability of gene to carry out role in cell and body; impact on fx -> affect on phenotype
SNP creation
damage not repaired properly and when DNA pol incorporates wrong nucleotide when copying genome
SNP in mitosis
some somatic body cells will differ from others
SNP in meiosis
“non-Mendelian event”; resulting offspring will differ from parent
SNP alleles
usually just 2 though 3 can happen; more frequent allele= major allele, less frequent allele= minor allele; which is major and which is minor can differ based on sample studied
“Fixed” for a given allele
A breed where only this allele is found never the other (ie if G and A allele and only find G allele in quarter horses never the A the QHs would be fixed for G allele)
private allele
2 alleles found in one breed but all other breeds only have one of those alleles so the second allele would be private to that breed (ie Shetland ponies have A and C alleles but all other horses only have A allele so C allele is private to Shetland pony)
SNP useful for maping
mutate at low rate compared to other sequence variants; also typically only two allele
Manhattan plot
map phenotypes of interest; use these for Genome wide association mapping studies (look at position of SNPs vs test value); simple plots for things like eye color harder with things with multiple factors such as body mass
SNP discovery
discovered by sequence alignment
How to calculate allele freqency
of “X” allele chromosomes/ (total # of case chromosomes)
remember to multiply # cases studied by 2 for total # case chromosomes because 2 chromosomes/ case
remember heterozygous will have 1 allele per case homozygous will have 2 or 0 depending on if you are examining dominant or recessive
Genome wide association mapping studies
genotype 10k-1M SNPs throughout genome; presence of each SNP is tested for association with a trait; looking for connection btwn phenotype and allele frequency at positions
polygenic
aka complex traits; multiple genes and environmental factors all contribute to make the trait value; vast majority of traits are complex; often are qualitative traits measured on continuum not yes no
ex. body condition
rhythmic motor behaviors in nature
- breathing
-locomotion
-stridulation - insect flight
Gate change (rhythmic motor behavior change in horses) due to a SNP in gene DMRT3 (Icelandic points Tolt); if mice have SNP change to DMRT3 gene (transcription factor) then they too have gate change
other variables in gate
- limb length
-length of neck - length of back
- center of gravity
these are all biomechanics showing interplay btwn SNP and biomechanics
SNP in cattle
causes leukocyte adhesion deffect in PM expressed protein (lack of leukocyte B2 integrin expression); all those with mutant allele related to one bull who sired a ton of calves via artificial insemination
maincoon cat familial hypertrophic cardiomyopathy
linked to SNP (cardiac myosin binding protein)
Indel variations
insertion or deletion that leads to difference in presence of absence of small or large stretch of sequence; less common than SNPs but can exert dramatic impacts on gene fx if occur in coding exon (especially if -> frameshift); some are v large and contain entire genes or pieces of genes or regulatory sequences for genes
copy number variations
CNVs/ strucutral variations/ copy number polymorphysms= large scale < 1kb differences in genome content; bias for effecting non-genetic sequences but effect genetic sequences as well; CNV is pervasive in genomes
alignment display convention with indels
put in *** for gap where insertion is in genes without insertion so they line up in computer though this is not what they look like in reality
what came first with indel
usually we can’t know which is ancestral state and which state is from insertion or deletion so not helpful for ancestral tracing
myostatin gene whipits
have 2 nucleotide sequence variation in myostatin gene due to indel inactivating myostatin gene (frameshift -> premature truncation of protein); if heterozygous run faster but if homozygous for mh/mh have too much muscle and slower with debilitating muscle cramps
microsatellites
short stretches of repeated sequence aka simple tandem repeats; DNA pol frequently makes mistakes when copying these repeats especially if track is long and simple; markers not used for mapping studies; sometimes they are direct cause of phenotype variation
microsatalites vs SNPs
microsatalites mutate at a higher rate; many alleles at each marker so they are highly informative though not used for mapping studies; easy to genotype by measuring length differences; amenable marker for genome wide scans; high mutation rate obscures relationship among alleles in population (many alleles identical by state but not by descent)
epilepsy
caused by small satellite repeats in some cases; look at PCR of this and can see repeats increase or decrease length of sequence; diff in length of primer gives rise to DNA products; homozygous and heterozygous get diff PCRs bc diff repeats lengths
CNV in sharpeis
more CNVs in chormosome 15 -> wrinkly face but also to periodic fevers but some healthy sharpeis have just as many CNVs showing impact of other genetic modifiers on how clinical phenotype being expressed
coat color variation in horess
from 4.6kb duplication (strong genetic singal highly correlative for this)
Mobile elements
interspersed repeats sequences and transposable elements can move themselves within genome and propagate independent of cellular replication; most are fixed for the insertion (all chromosomes in species carry the insertion) but some -> allele differences (segregating for insertion/ non-insertion); ubiquitous; account for substantial quantity of genetic material
phenotype mobile genetic elements
mobile genetic elements can -> phenotype change
narcolepsy doberman
caused by gene disruption via short interspersed element (type of transposon) of gene that codes for GCPR
Chondrodysplasia in domestic dogs
retrotransposon is associated with breed-defining chondysplasia in domestic dogs (FgF4 retrogene)
transposable elements
endogenous viruses; these = mobile elements
intervertebral disk displacement
example of retrotransposons encoding fibroblast growth factors; also shown in some skeletal deformations in humans; this is bc of diff patterns of growth factors
Long interspersed elements (LINE), short interspersed elements (SINE)
retrotransposons that exist at high copy in mammalian genome; these can integrate into gene disrupt it and cause change in phenotype; 1/2 of all annotated canine genes contain SINE repeats
merele patterns in domestic dogs
from retrotransposon insertion (SILV); heterozygous is merel homozygous recessive is white
Canine transmissible venereal tumor
associated with LINE insertion bc oncogene
genomic DNA sequences differ between
species, breeds, sub-populations, individuals
sequence differences (markers) w in individuals of a species can be used to
map traits
most sequences variation function
no apparent function
sequence variations contributing to trait differecnes
have clinical relevance such as disease
phenotype/ dx causing mutations an be
SNPs, indels, and many other kinds variations
