Genetic markers Flashcards
what is a genetic marker
some feature in the genome that allows us to differentiate between different alleles
uses of genetic markers
forensics (crime scenes, paternity tests, conservation genetics)
GWAS and QTL analysis to evaluate whether markers are associated with phenotypic variation
measuring genetic variability
reduced representation methods
measure variation at intervals rather than sequencing entire genome
copy number variation
type of structural variation in the genome where sections of DNA are repeated, and the number of repeats varies between individuals
not detected in traditional sequencing methods
can create phenotypic variation
copy number variation detection
measure level of sequence coverage
coverage
how many sequence reads there are in the genome. if there is a deletion or duplication, there will be fewer or more sequences detected
allozymes
different forms of an enzyme that are encoded by different alleles at the same locus
Differ in electric charge, which affects
migration through an electric field
Detected with enzyme-specific stain
noticed variation in the same protein across individuals
RFLP
undegraded DNA cut into fragments using specific restriction enzymes
fragments differ in length because of differences in number of large DNA repeats (VNTRs) which changes the distance they migrate in the gel
microsatellite loci
short tandem repeats
highly polymorphic
highly abundant
can distinguish many alleles at a locus as alleles differ in the number of repeats
more repeats=shorter distance on gel
variation at microsatellite loci
huge variation due to high mutation rate
slippage-misalignment of strands
backwards slippage of newly forming strand causes..
insertions of repeat
forward slippage of template strand causes..
deletion of repeat copy
haplotype in terms of SNPs
haplotype is the specific set of SNPs and other genetic variants observed on a single chromosome or part of one. SNPs within a haplotype are physically linked and tend to be inherited together. new haplotypes can arise through mutation or crossing over which breaks up the sets of SNPs. rate of crossing over is proportional to the physical distance between genes. the nonrandom association between genetic variants within a haplotype is called linkage disequilibrium.
uses of SNPs
track haplotypes
infer variation
GWAS
Studies almost always based on comparing alternative alleles at
SNP loci across the genome
infering haplotypes using SNPs
if you know the SNP at one allele, can infer the rest as they are close together
using a subset of SNPs to infer rest of genome
too far apart and recombination mixes them so cant infer one from the other
studies of linkage disequilibrium with SNPs
recombination is not random
there are hotspots where it occurs more by chance
SNPs and evolution
distribution of SNPs provides information about regions of the genome that have evolved quickly in the recent past-shows how humans respond to natural selection
SNPs and disease
when an SNP is physically close to a disease-causing locus, it will tend to be inherited along with the disease-causing allele so people with the disease tend to have SNPs near the disease-causing gene that are different from those of healthy people. (the SNPs dont normally cause the disease but are linked to disease-causing alleles).
genealogy
idea that if you take all individuals now and trace them back in time all lineages will eventually coalesce to a common ancestor
SNPs in ancestry
SNPs reflect ancestry of haplotypes
can infer from a set of haplotypes the ancestry
different lineages show variation at linked SNPs
low coverage sequencing
Sequence individuals at very low
coverage (coverage is the average
number of ‘reads’ per base of genomic
DNA)
missing sequences inferred from known
used to infer haplotypes
mitochondrial markers features
no recombination
uniparental inheritance
haploid
highly polymorphic sequences
can capture different evolutionary histories
maternal lineages
used in genotyping arrays
genotyping arrays
Set of SNP loci identified
K-mer probes developed that bind to DNA– hybridisation of DNA to spots on array identifies genotype
pros of genotyping arrays
low error rate– low cost per sample (especially when using existing arrays)– reliable and comparable results from each individual
cons of genotyping arrays
requires adequate information on SNP loci
costly to create a new array
fixed set of SNPs may not be representative of all variation in a population
biased to reference group used to identify the SNPs
illumina infinium assay
identifies SNPs
silica bead in wells of etched array have probes attached
specific SNPs hybridise to probes
(Sequence stops one base-pair from the SNP location)
Single base extension adds a fluorescently labelled base to SNP position
SNPs in infering ancestries
populations differ in SNP frequencies and pattern of SNPs that are linked together along the chromosome
can find pattern of migration of humans
genetic diversity is ….. in more recently founded populations
lower, isolation by distance
chromosome painting
used to assign different ancestries or genealogies to specific regions of the genome based on SNP (Single Nucleotide Polymorphism) information. This technique helps visualize how different chromosome regions have distinct evolutionary histories.
