Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

GEN > Discovery of Human Disease Genes > Flashcards

Discovery of Human Disease Genes Flashcards

1
Q

What causes most disease states and traits?

A

Combo of gen and env factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Give e.g.s of diseases mainly driven by gen

A
  • achondroplasia

- CF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give e.g. of diseases mainly driven by env

A
  • chicken pox
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Give e.g.s of diseases caused by both gen + env

A
  • psoriasis

- Chron’s Disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why do we want to identify disease-causing genes?

A
  • molecular confirmation of clinical diagnosis
  • accurate carrier testing for indiv/couples
  • pre-symp testing for adult onset cond e.g. HD, familal breast cancer
  • prenatal diagnosis for pregnancies at high risk of sever disorder
  • provides insight into pathological mech underlying disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 3 steps of pos cloning?

A
  1. identify multigen affected pedigree - collect DNA of family members
  2. systematic evaluation of inheritance patterns across genome
  3. multinational search within genomic regions coseg with the disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are monogenic diseases caused by?

A

Mutation in a single gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What things is nec and sufficient to produce clinical phenotype?

A

Mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What do monogenic disorders demonstrate in pedigrees?

A

Dom/rec inheritance patterns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why is more known about mol basis of human phenotypes now than in the past?

A

Advances in DNA seq tech

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What causes auto dom diseases?

A

Mutations in 1 copy of gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are auto dom cond inherited?

A

Vertical transmission - affected indiv must have 1 of 2 affected parents/de novo mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are 2 key features of auto dom inheritance?

A
  1. equal no. of M + F affected

2. M to M transmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the phenotype of unaffected indiv iffspring of auto dom cond?

A

Unaffected - but may arise as new mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How are auto rec cond inherited?

A

Mutations in both copies of gene nec to cause disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is phenotype of carries of auto rec cond?

A

Generally clincally normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are 2 key factors of auto rec inheritance?

A
  • equal no. of affected M + F

- consanguinity may be present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How are X-linked rec disorders inherited for M + F?

A

M - mutations in 1 copy of gene

F - mutations in both copies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are 2 key features of X-linked rec inheritance?

A
  • incidence much higher in M than F

- no M to M transmission - as M passes on Y chr

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

During meiosis, what is role of precursor cells of sperm/ova?

A

must multiply and at same time dec no. of chr to 1 full set

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What happens in process of recomb?

A

2 chr of homologous pair exchange segments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does freq of recomb between 2 locations on chr depend on and why?

A

Distance - bc recomb can occur at location along chr

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is genomic linkage?

A

Genes close/DNA regions close together on the same chr more likely to be co- inherited than genes/DNA regions further apart

24
Q

How is genomic linkage observed experimentally?

A

By assessing genomic loci that vary within pop + evaluating their co-inheritance

25
What can be said about distance of these 3 variants loci based on this info: - 11 informative meiosis - 11 recomb events observed - 8 recomb events between A + B - 3 recomb events between B + C
B is closer to C than A to B bc there are less recomb events between B + C so they must be closer together (linked)
26
How can seg be used to map disease genes with linkage?
- can reconstruct mutation genotype without actually knowing where mutation locus is - when discover new mutation, look for linkage to other genes to determine location of mutation on a chr + help identify mutated gene - can then consider series of variable loci across genome and see if they're linked to mutation locus
27
What can be said about the mutation locus based on coseg with variant locus A (use lecture diagram): - observe inheritance of the mutation twice with allele A1 - twice with allele A2
Mutation locus not linked to locus A - should be consistency of same allele being inherited with disease and too many recomb events
28
What can be said about the mutation locus based on coseg with variant locus B: - inheritance of mutation 3x with B1 and 1x with B3
Mutation locus nearly linked to B as there's little recomb events
29
What can be said about the mutation locus based on coseg with variant locus C: - inheritance of mutation everytime with C1 and never when disease not transmitted
Mutation locus linked to locus C and mutation located close to variant locus C
30
What is linkage process typically used to assess, how and why?
- Seg of genomic regions using aprrox 400 multiallelic loci aka microsatellite repeats/approx 5000 biallelic loci (usually SNPs). - approach enables systematic evaluation of coseg of genomic regions with disease locus
31
What statistical is used to detect presence of linkage?
- LOD score which estimates whether 2 genes/gene + a disease gene are likely to be located near each other on a chr + therefore likely to be inherited - Evaluate likelihood ratio that those genotypes occurred under hypothesis that there's linkage between marker (look at seg of alleles from each marker) + trait (look at seg of trait within family)
32
How is the LOD test score interpreted?
- LOD score >3 consistent with linkage (2 genes located close to each other on chr) - odds are 1000:1 that 2 genes linked and therefore inherited together - LOD score
33
What are the next steps once linkage to chr region has been identified?
- identify genes located within linkage interval - assess genes as pot candidates based on their bio functions - seq genes in affected indiv to try to identify causative mutation
34
What is result of establishing coseg of specific genomic regions with transmission of disease phenotypes in pedigrees?
Poss to locate genomic region where disease-causing gene resides
35
Why is it nec to seq genes in linkage interval?
coseg region (linkage interval) likely to contain more than 1 gene so need to seq to identify causative mutation
36
Why may genes in linkage interval be sequenced?
To attempt to identify causative mutation
37
What 2 things can linkage analysis in single pedigree be confounded by?
1. Non-penetrance | 2. Phenocopies
38
What is non-penetrance?
Indiv has mutation but won't dev disease
39
What are phenocopies?
Indiv has something that resembles disease but don't have disease-causing mutation
40
Where may linkage analysis also be performed and what issue can arise from results?
In multiple pedigrees and results combined has a confounding issue of gen heterogeneity
41
What is gen heterogeneity?
Same/similar phenotypes caused by mutations in multiple genes
42
Why have DNA seq costs dec?
- Becoming more affordable to just seq protein coding regions of genome (exome seq)
43
What are adv of exome seq?
- ability to undertake affordable whole genome seq allow ' genome informed' personalisation of care - also allows opportunity for identification of diseases causing genes
44
What is size, no. variants and cost of human genome?
Size: approx 3 bn bp No. of variants: approx 3m Cost: approx £1000
45
What is size, no. variants and cost of human exome (all protein coding regions)?
Size: 30-50m bp No. of variants: approx 20 000 Cost: £300-£800
46
Based on the figs, why is it more cost effective to seq exome for mongenic disease?
- More cost effective and rep only approx 1% - whilst some exceptions, causative mutations in monogenic diseases consistently identified in ortein coding region of genome (exome)
47
What can be found by seq the exome?
- catalogue all protein altering variation in an indiv - if indiv has monogenic disease, can filter through this variation to identify which variant is causing disease - allows new e.g.s for disease gene identification
48
How can exome seq help with identifying disease causing variants?
- Seq 3 people's exomes and identify pos in exomes to see where they varied - identify genes with hetero protein altering variants and therefore find allele passed on from 3 variants identified
49
What has dramatic decrease in price of DNA seq provided?
New methods to identify disease causing genes
50
What are the new methods of identifying disease causing genes?
- filtering affected indiv variant profile to exclude variants unlikely to play role in disease - comparison between filtered variant profiles from unrelated affected indiv to identify genes that are site of candidate variation in multiple indiv
51
What are the new methods of identifying disease causing genes not reliant on?
Ascertainment of large pedigrees
52
What is the formula for the LOD score?
LOD = log10 [L(linkage)]/[L(no linkage) LOD score = log10 x likelihood that genotype occurred under hypothesis that there's linkage/likelihood that genotype occurred under hypothesis that there's no linkage
53
When are genes not linked?
- genes on sep chr never linked | - genes far away on the same chr
54
Explain how linkage works using an e.g. in genes that are not linked
- gene 1 and 2 on same chr and far apart - each gene has 2 alleles (A+B) so have 1A + 2A on one pair and 1B + 2B on other - bc gene 1 + 2 far apart, more likely to be recomb evet between them so gametes end up with new allele combos not present in parent - gene 5 + 6 on sep chr but never linked - each gamete gets single copy at random of each chr + bc there's nothing holding them together, alleles can pass to gametes in any combo
55
Explain how linkage works using an e.g. in genes that are linked
- gene 3 + 4 sit closer together on same chr - 3A + 4A on 1 pair + 3B + 4B on other - therefore less likely recomb event happen between them - most of the time, 3A + 4A stay together + therefore inherited together as well as 3B + 4B

GEN (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions