Identifying Genetic Causes of Disease Flashcards Preview

Core Lectures > Identifying Genetic Causes of Disease > Flashcards

Flashcards in Identifying Genetic Causes of Disease Deck (62):
1

Why is it important to understand how disease is inherited?

For genetic testing and counselling
For risk prediction

2

Why is it important to elucidate the molecular basis of disease?

To identify drug targets
For 'personalised medicine'
For gene therapy

3

Define allele

A version of a gene
(Humans are diploid so have two alleles)

4

Define homozygous

Two copies of the same allele (AA or aa)

5

Define heterozygous

Two copies of different alleles (Aa)

6

Define hemizygous

The state when only one allele is present

7

Define autosomal inheritance

A trait carried on one of the autosomes (non sex chromosome)

8

Define sex-linked inheritance

A trait carried on either the X or Y chromosome

9

Define mitochondrial inheritance

A trait carried within the mitochondrial (non nuclear) DNA and is maternally inherited

10

Define monogenic trait

Alterations to one gene causes phenotype

11

Define polygenic trait

More than one gene determines phenotype

12

Define multifactoral/complex trait

More than one gene determines phenotype and environmental factors may also have a role

13

Define dominance

Only one copy of an allele is required to cause a phenotype (heterozygous and homozygous individuals are affected)

14

What does a solid shape in a pedigree indicate?

An affected indivual

15

Define incomplete penetrance

Where individuals who have the 'faulty' copy of the gene do not display the disease or phenotype
This can show as skipped generations in pedigree analysis

16

Give an example of a codominant trait

Human blood group

17

Define codominance

Both phenotypes are expressed

18

What can monogenic traits be seen by?

Pedigree analysis

19

What type of inheritance do monogenic traits follow?

Simple Mendelian inheritance

20

How can you tell if a disease is genetically determined?

See if the disease runs in families

21

What can we deduce about parents if an affected individual has an autosomal dominant disease?

They must have at least one affected parent

22

What percentage of offspring will be affected if a parent has an autosomal dominant disease?

Approx. 50%

23

What is the ratio of males and females affected by an autosomal dominant disease?

Equal

24

Both males and females can transmit an autosomal dominant phenotype to their offspring, true or false?

True

25

What percentage of offspring are unaffected when both parents are heterozygous and affected by an autosomal dominant disease?

~25%

26

What percentage of offspring are affected when both parents are heterozygous and affected by an autosomal dominant disease?

~75%

27

What percentage of offspring have one copy of the dominant allele when both parents are heterozygous and affected by an autosomal dominant disease?

~50%

28

What percentage of offspring have two copies of the dominant allele when both parents are heterozygous and affected by an autosomal dominant disease?

~25%

29

For a carrier and unaffected parent of an autosomal recessive disease, what is the ratio of unaffected, affected and carrier offspring?

50% unaffected
50% carrier

30

For an affected and unaffected parent of an autosomal recessive disease, what is the ratio of unaffected, affected and carrier offspring?

100% carrier

31

When both parents are carriers of an autosomal recessive disease, what is the ratio of unaffected, affected and carrier offspring?

50% carrier
25% affected
25% unaffected

32

X-linked recessive diseases have the same principle as autosomal recessive diseases, but what else should be considered?

The inheritance restrictions of sex chromosomes
Males only have one copy of X so will show the recessive phenotype

33

For an affected father and carrier mother of an X-linked recessive disease, what is the ratio of unaffected, affected and carrier offspring?

Females:
~50% affected
~50% carrier
Males:
50% affected
50% unaffected

34

For an unaffected father and carrier mother of an X-linked recessive disease, what is the ratio of unaffected, affected and carrier offspring?

Females:
~50% unaffected
~50% carrier
Males:
50% affected
50% unaffected

35

For an unaffected father and affected mother of an X-linked recessive disease, what is the ratio of unaffected, affected and carrier offspring?

Females:
100% carrier
Males:
100% affected

36

List the types of genetic variation

Chromosomal abnormality, e.g. translocations, trisomy
SNPs (single/simple nucleotide polymorphisms), e.g. A to T
Copy number variation (CNV)
Indels (insertions or deletions)

37

What is the candidate gene approach for identifying genetic causes of disease?

Look for/type variants in gene regions where known biology predicts involvement
Sequence (whole genome or exome) genes

38

What is the downside to the candidate gene approach for identifying genetic causes of disease?

It is biased as it relies on prior knowledge of disease biology

39

What do regional association plots show?

The linkage relationship between SNPs

40

How can the location of a SNP influence disease?

Could be...
In a coding region (changes protein produced)
Intronic (splicing)
In a regulatory region (promoter, enhancer)

41

Do common diseases often run in families?

Yes

42

Do complex traits follow Mendelian ratios of inheritance?

No

43

How many genes are involved in complex traits?

Multiple

44

Complex traits are purely genetic, true or false?

False, they also have environmental determinants

45

What is now the most common method for investigating the genetic basis of complex diseases?

Genome-wide association studies (GWAS)

46

Why is GWAS unbiased?

Because the whole genome is tested

47

What does GWAS allow the discovery of?

Genetic regions with previously unknown disease biology

48

What do modern GWAS arrays type individuals for?

SNPs, indels and CNVs

49

How many variants per individual have been identified using GWAS arrays and imputation?

~10 million

50

How can you analyse the genes that may potentially be involved with a disease?

Using case-control analysis

51

What is the basis for case-control analysis?

Compare individuals with the disease (case) to healthy individuals (control)

52

What is the standard threshold for genome-wide significance and what is this based on?

p < 5E-8
Based on Bonferroni correction for 1 million independent tests

53

What is the false discovery rate for genome-wide significance?

1% or 5%
FDR 0.01 - 1 in every 100 loci incorrect
FDR 0.05 - 5 in every 100 loci incorrect

54

How many variants is genome-wide significance testing?

Millions of variants across thousands of people

55

Why do you need to control for multiple testing of genome-wide significance?

To reduce false positive results

56

How does the location of the gene influence disease?

Most disease associated SNPs affect genes in close proximity (~200kb)

57

How does the location of the SNP influence disease?

Knowing/predicting which SNP is having the effect can help identify the gene involved

58

What questions can bioinformatics analysis answer to help predict the function of a SNP?

Is a protein coding change deleterious to protein function?
Is a transcription factor binding site altered?
Is there evidence of changes in gene expression linked to the SNP?

59

Why is bioinformatics analysis helpful?

As there is an increasing amount of publically available data and online tools

60

Understanding how a disease is inherited can help identify whether it is...

Monogenic or complex

61

GWAS is a common and unbiased approach now widely used to identify genetic causes of disease, true or false?

True

62

What does GWAS help us to identify about a disease?

Risk prediction
Biological mechanisms involved
Personalised medicine (in the future)