Linkage Analysis

Question 1

What is a haplotype?

Answer 1

A group of alleles that are inherited together from a single parent

Question 2

What are the three groups of genetic disease classification?

Answer 2

Mendelian / monogenic,
Non-mendelian /polygenic,
Multifactorial

Question 3

What is a mendelian/ monogenic disease?

Answer 3

disease caused by a single gene with little or no impact from the environment
super rare but high penetrance

Question 4

What is an example of a mendelian/monogenic disease?

Answer 4

PkD

Question 5

What is a non-mendelian/polygenic disease?

Answer 5

Diseases or traits caused by the impact of many different genes, each only having a small individual impact on the final condition
common but low penetrance

Question 6

What is an example of a Non-mendelian /polygenic disease?

Answer 6

Psoriasis

Question 7

What is a multifactorial disease?

Answer 7

Diseases or traits resulting from an interaction between multiple genes and offer multiple environmental factors

Question 8

What is an example of a multifactorial disease?

Answer 8

Heart disease

Question 9

What is a linkage analysis?

Answer 9

methods used to map the location of a disease gene in the genome

Question 10

What do linkage analyses do?

Answer 10

use genetic markers to identify the location of a disease gene based on it’s physical proximity

Question 11

What do genetic maps do?

Answer 11

look at information in blocks or regions

Question 12

What is a centimorgan?

Answer 12

The percentage chance of recombination

Question 13

What do physical maps do?

Answer 13

Provide information on physical distance between landmarks based on their exact location

Question 14

What is genetic linkage?

Answer 14

The tendency for alleles at neighbouring loci to segregate together at meiosis

Question 15

When are crossovers more likely to occur?

Answer 15

When loci are separated by distance

Question 16

Where must loci be in relation to one another to be linked?

Answer 16

Very close together

Question 17

How long does a whole genome scan for GWAS using SNPs take?

Answer 17

> 2-3 months

Question 18

How long does a whole genome scan for GWAS using microsatellite markers take?

Answer 18

<1-2 months

Question 19

What type of system is the SNP GWAS based on?

Answer 19

Microarray based

Question 20

What type of system is the microsatellite marker GWAS based on?

Answer 20

PCR based

Question 21

What is microsatellite genotyping generally used for?

Answer 21

DNA printing from very small amounts of material, paternity testing and Linkage analysis for disease gene identification

Question 22

What does fluorescent genotyping allow for?

Answer 22

multiplexing of PCR products with different colours and fragment lengths

Question 23

What resolution are fragment sizes separated down to in fluorescent genotyping?

Answer 23

1 bp resolution

Question 24

Are SNPs causal disease variants?

Answer 24

No

Question 25

In SNP genotyping microarrays, what are alleles identified by?

Answer 25

relative fluorescence

Question 26

What are SNP genotyping microarrays generally used for?

Answer 26

linkage analysis in families and GWAS in populations

Question 27

If a Marker is linked to a disease locus, how much of the time will the Same marker alleles be inherited by two affected relatives?

Answer 27

More often than expected by chance

Question 28

If a Marker and the disease locus are unlinked, what is the chance the affected relatives in a family will inherit the same marker alleles?

Answer 28

Less likely

Question 29

How do you build a haplotype?

Answer 29

By determining which allele is inherited from which parent

Question 30

How can you tell where a recombination event happened?

Answer 30

The inherited gene switches onto the other arm of the parental genotype

Question 31

What does LOD stand for?

Answer 31

Logarithm of the odds

Question 32

How can you assess the probability of linkage

Answer 32

A LOD score

Question 33

What does a LOD score do?

Answer 33

Assesses the probability of getting the same data if the two loci are linked compared to getting the same data by chance

Question 34

What is a recombination fraction?

Answer 34

The proportion of recombinant births

Question 35

What does a high LOD score mean?

Answer 35

There is a high likelihood of linkage

Question 36

How is a LOD score calculated?

Answer 36

Using genotype data for many genetic markers in multiple members of a family

Question 37

What do parametric analysis specify?

Answer 37

The pedigree structure and inheritance pattern

Question 38

What does a non-parametric analysis detect?

Answer 38

Allele sharing between affected individuals

Question 39

What will happen if different families are linked to the same disease locus?

Answer 39

Increase the overall score because LOD scores are additive

Question 40

What LOD score is considered evidence for linkage?

Answer 40

>3

Question 41

What LOD score is considered evidence against linkage

Question 42

What is a critical linkage interval?

Answer 42

Where a diseased gene is found

Question 43

What type of genetic mutation is Adams-Oliver syndrome?

Answer 43

Autosomal dominant

Question 44

What are the two clinical signs of Adams-Oliver syndrome

Answer 44

Terminal transverse limb defects and scalp aplasia cutis congenita

Question 45

What are terminal transverse limb defects?

Answer 45

Truncation of the hands or feet

Question 46

What is scalp aplasia cutis congenita?

Answer 46

Loss of skin on the scalp

Question 47

What are other associated features of Adams-Oliver syndrome?

Answer 47

Neurological anomalies, cardiac malformations and vascular defects

Question 48

Where is the defect that causes Adams - Oliver syndrome according to linkage analysis found?

Answer 48

Chromosome 3

Question 49

What is the defect that causes Adams - Oliver syndrome according to linkage analysis?

Answer 49

Heterozygous mutations of a gene detected in two unrelated probands, causing a premature stop codon