EBH 302 Test 1

mutation

broad term for a change to the DNA sequence

alleles

alternate forms of a gene or specific DNA sequence at a given locus

variant

one of the multiple alleles at a given genomic position

genetic polymorphism

used to refer to variants above 1% frequency in the population

neutral allele

do not affect the evolutionary fitness of a carrier, often with no phenotypic effect at all

exon sequencing

sequences exons and its flanking regions, including intronic splice sites, UTRs and nearby intergenic sequence

enhancers

bind to transcription factors, increasing the rate of transcription, sequence variation can modify effectiveness, often found upstream (5’) of transcription start site

non-coding DNA

sequence not in a protein coding gene, includes: introns and intergenic regions (pseudogenes, retrotransposons: LINEs, SINEs), much of it is transcribed

non-coding RNA

functional RNA molecule that is transcribed, but not translated, includes microRNA

microRNA

short non-coding RNA that act on mRNA, 1000s have been identified within introns and intergenic regions, after binding to complementary mRNA, they may prevent translation or facilitate mRNA degradation (gene silencing)

Long interspersed nuclear element (LINE)

retrotransposon that spans 6-8 kb and encode their own reverse transcriptase (e.g. L1 element)

retrotransposon

genetic element that is transcribed to RNA, then reverse transcribed back into the DNA (i.e. LINEs and SINEs)

Short interspersed nuclear element (SINE)

retrotransposon that spans 100s of bp, reverse transcribed through target-primed reverse transcription (using other proteins, not its own reverse transcriptase) (e.g. Alu element)

telomere

repetitive DNA sequence at the end of chromosomes

segmental duplications

nearly identical sequence that exists in multiple locations

structural variants

variation in chromosomal structure (50bp-3Mb), based in duplication, inversion, insertions, etc…

mitochondrial genome (mtDNA)

short, circular DNA molecule (16.5 kb in length), 1000s of copies per cell, 37 protein coding genes (no introns, almost no intergenic region, 1 transcript from each strand), not packaged, maternally inherited, no recombination

autosome

22 diploid chromosomes, recombination

x-chromosome

female typically has two copies, male typically has one copy, recombination during maternal meiosis

y-chromosome

male typically has one copy, paternally inherited, recombination with X-chromosome is limited

haplotype

a combination of allelic states of a set of polymorphisms lying on the same DNA molecules (not the same as genotype). Variation comes from mutation and/or recombination. Lack of recombination simplifies identifying ancestral relationships

haplogroups

a set of haplotypes that share recent common ancestry, haplotypes that have a high number of shared-derived alleles

AIMs (Ancestry Informative Markers)

SNPs that are statistically associated with certain modern populations

microsatellites

short tandem repeats (STRs)

repeats of 1-7 bp

change in number of repeats occurs because of slippage during DNA replication

stepwise mutation model (SMM)

the number of repeats increase by +1 or -1 in the germline, no jumping from like 3 → 7 repeats

DNA slippage

theoretical origin of microsatellite variation

multiplexing

PCR amplification of multiple sequences simultaneously

transition

pyramidine to pyramidine or purine to purine, appears more frequently

transversion

pyramidine to purine or vice versa

misincorporation

cause of base substitutions, error during DNA replication

frequency 1×10^-9 to 1×10^-11 per nucleotide per replication

mutagenesis

cause of base substitutions, alteration by chemical or physical processes

identity by descent

two individuals/species share an allele inherited from a common ancestor

identity by state

two individuals/species share an allele that was independently derived

hypervariable segments

part of mtDNA control region, early sequencing target for study of mtDNA diversity

reversion

substitution back to ancestral state

recurrent

independent substitutions resulting in identity by state

pedigree based (mutation rate)

direct estimate, counts mutations between generations

phylogeny based (mutation rate)

indirect estimate, assumes most mutations are neutral, divide differences between species/populations by time since divergence. ability to sample a few individuals and still have lots of mutations but problem is the calibration point from non-genetic information