Genome Organization and Variation Flashcards
When you compare an individual’s genome to a reference genome…
Individuals have 3-4 million single nucleotide changes
Single Nucleotide Variants (SNVs)
refer to any single nucleotide change in the genome
Functional SNV
leads to amino acid change (affect protein function)
Missense variants
change of an amino acid
non-sense variants
change an amino acid to a stop codon
Stop loss variants
lead to loss of the stop codon
T or F: There are functional variants that disrupt a splice site
TRUE
Non-functional SNV
no amino acid change (no effect on protein functions)
Silent variants (non-functional)
change a nucleotide but not the amino acid
Intronic variants (non-functional)
Introns
Intergenic variants (non-functional)
between genes
SNPs (single nucleotide polymorphism) definition
polymorphisms that occur in at least 1% of the population (more common than SNV)
Mutation
change in genome more rare than SNP;
usually refer to a change which results in a phenotype
Small insertions or deletions of up to 20-30 bases are called:
Indels (insertion/deletion);
vary in size, multiples of three are most common since they do not disrupt the reading frame
Short Tandem Repeats (microsatellites)
2-12 nucleotides that can be present in 10-100 copies; more common than SNPs
There are a lot of variations in the number of repeats of microsatellites due to:
errors during replication when polymerase slips
T or F: Microsatellites can be used in forensics and linkage studies?
TRUE
Transposons and retrotransposons are…
mobile DNA sequences
Retrotransposons definition
copied into an RNA intermediate before they are reverse transcribed and inserted into the genome
LINE (long interspersed repetitive elements)
encode the elements necessary for retrotransposons to make copies and insert into the genome;
17% of genome
SINEs (short interspersed repetitive elements)
10% of genome;
300 bp long;
from retrotransposons
LTRs (long terminal repeats)
several kilo bases in size and represent around 8% of genome;
from retrotransposon
Retrotransposons/transposons pose a risk because…
can replicate and insert into the genome in places that cause harm
Copy number variants (CNVs)
deletions or duplications of part of the genome that can range from 100 bp to an entire arm of a chromosome;
can be found at higher resolution than karyotyping
Although inversions and translocations are large structural variations, they…
DO NOT AFFECT COPY NUMBER OF GENES
Inversions definition
pieces of DNA that invert in the genome often due to recombination between repeats
Translocations
exchanges of DNA between chromosomes
______ can be used to map and find mutations that cause disease
Variants
2 types of genetic mapping
- map based strategy which uses a set of markers spread throughout the genome
- direct approach of looking at the causal variants through genome or exam sequencing
Linkage Studies
Use micro satellites;
DNA from family and sequences of 300-400 micro satellites are compared between affected and unaffected family members;
microsats that are more prevalent in the affected than unaffected are close enough to the disease allele that recombination has not occurred between them;
evaluation of microsats in the area can narrow down the portion of the genome containing the disease allele further
Linkage Studies are successful at …
Identifying rare, inherited variants which are associated with severe disease in families
GWAS (genome-wide association studies)
Genetic mapping using SNPs;
Advantage to GWAS is that studies can include populations and not just families;
must be large sample size and well defined phenotype
Genome sequencing
Identify causal variants directly;
does not limit the type of variation that an be detected or inheritance pattern that can be studied;
Challenging to interpret large amounts of data
