Human Genetic Variation (EBI)

Question 1

What are sources of genetic variation?

Answer 1

mutation and recombination

Question 2

What is DNA mutation?

Answer 2

A permanent alteration to a DNA sequence. It arises as an error during DNA replication and is fixed in DNA.

Question 3

What is a variant?

Answer 3

A specific region of the genome which differs between two genomes.

Question 4

What are alleles?

Answer 4

Different versions of the same variant.

Question 5

What is a reference allele?

Answer 5

The base that is found in the reference genome. It doesn’t have to be the major allele.

Question 6

What is an alternative allele?

Answer 6

Any base, other than the reference, that is found at that locus.

Question 7

What are haplotypes?

Answer 7

Blocks of alleles that are close together on the same chromosome and tend to occur together more often that is expected by chance.

Question 8

What is linkage disequilibrium (LD)?

Answer 8

The measure of how often two alleles or specific sequences are inherited together.

Question 9

What is a mendelian trait?

Answer 9

A trait that is controlled by a single locus.

Question 10

What are complex phenotypes?

Answer 10

Traits influenced by multiple variants along with environmental factors.

Question 11

What is an SNP?

Answer 11

Single nucleotide polymorphism - single base-pair substitution.

Question 12

What are types of SNPs?

Answer 12

transition
transversion

Question 13

What is a transition SNP?

Answer 13

Interchange of the purine (A/G) or pyrimidine (C/T) nucleic acids.

Question 14

What is a transversion SNP?

Answer 14

Interchange of a purine and pyrimidine nucleic acit (e.g. G to T).

Question 15

What is an indel?

Answer 15

Insertion or deletion of a single stretch of DNA sequence from 2 to 200 base-pairs in length.

Question 16

What is a structural DNA variation?

Answer 16

A variation that occurs over a larger DNA sequence.

Question 17

What are the 5 most common types of structural variations?

Answer 17

isertion
deletion
inversion
duplication
copy number variation

Question 18

What can be the effects of variants on codons?

Answer 18

synonymous/silent
nonsense
missense

Question 19

What does it mean that a variation has a synonymous/silent effect on a codon?

Answer 19

A change to a redundant codon which codes the same amino acid. E.g. a change from GCT to GCC will still encode alanine.

Question 20

What does it mean that a variation has a nonsense effect on a codon?

Answer 20

A variant turns a coding codon to a stop codon. This results in a truncated protein which may or may not be subject to nonsense-mediated decay.

Question 21

What does it mean that a variation has a missense effect on a codon?

Answer 21

A variant changes the amino acid.

Question 22

What are in-frame indels?

Answer 22

Indels with length divisible by three (i.e. whole codon indels) in coding regions that cause insertions or deletions of whole amino acids into the proteins.

Question 23

What is a frameshift?

Answer 23

If the length of an indel is not divisible by three all codons downstream of the indel are shifted.

Question 24

What are TFBMs?

Answer 24

Transcription factor binding motifs. These are genomics sequences that specifically bind to transcription factors.

Question 25

What are transcription factors?

Answer 25

Proteins that regulate the transcription of genes and consequently gene expression.

Question 26

What is a missense?

Answer 26

A genetic alteration in which a single base pair substitution alters the genetic code in a way that produces an amino acid that is different from the usual amino acid at that position.

Question 27

What is a splice site variant?

Answer 27

A genetic alteration in the DNA sequence that occurs at the boundary of an exon and an intron (splice site). This change can disrupt RNA splicing resulting in the loss of exons or the inclusion of introns and an altered protein-coding sequence. Also called splice-site mutation.

Question 28

What is a stop-gain variant?

Answer 28

A DNA variant (or mutation) that changes at least one base of a codon, leading to a premature stop codon. (A “stop” codon is gained.) This, in turn, results in premature cessation of translation of messenger RNA into protein, and often an unstable, nonfunctional protein product.

Question 29

What is a stop-loss variant?

Answer 29

Single base-pair exchanges that happen within translational termination codons, which could result in the continued translation of the messenger RNA into the 3′ UTR.