Week 8: Identify Disease Genes and Genetic Susceptibility to Complex Diseases

Question 1

What is a big challenge in diagnosis?

Answer 1

to identify genes underlying complex (multifactorial) diseases, in which there is no obviously predominant disease locus

Question 2

Monogenic

Answer 2

influenced predominantly by a single gene locus

Question 3

Oligogenic

Answer 3

disease phenotype may be dependent on a few genes

Question 4

Polygenic

Answer 4

multiple genetic factors determine the phenotype, each making a small contribution

Question 5

Examples of Polygenic diseases

Answer 5

Type 1 and 2 diabetes, Coronary artery disease, Stroke, Rheumatoid Arthritis, Alzheimers disease

Question 6

Genetic risk factor

Answer 6

DNA variants have increased susceptibility of complex diseases

Question 7

Protective Factors

Answer 7

DNA variants shown to lower disease susceptibility

Question 8

Karyotype

Answer 8

A test that examines chromosomes in a sample of cells, usually in metaphase or pro metaphase, when the chromosomes are most condensed

Question 9

Benefits of Karyotyping

Answer 9

cheap, easy, viable

Question 10

Disadvantages of Karyotyping

Answer 10

takes long time and less resolution

Question 11

Chromosome FISH

Answer 11

fix chromosome preparations on microscope slides, treat the slides to denature DNA, and hybridize fluorescently labeled probes of interest to denatured DNA

Question 12

Exome Sequencing

Answer 12

Collection of all exons in the genome and sequencing them

Question 13

Why do we use exome sequencing?

Answer 13

1. When we don’t know the cause of genetic disease
2. Patients with rare disease of unknown cause
3. Patients who have disease but unknown as to how they got it

Question 14

Benefits of Exome sequencing

Answer 14

cost effective and less laborious, easier than whole genome sequencing

Question 15

Genetic Linkage

Answer 15

alleles at very closely neighboring loci (<50 map units) on a DNA molecule are co inherited because the chance they are separated by recombination is very low

Question 16

What test do we use to determine gene linkage inheritance

Answer 16

Logarithm of Odds (LOD)

Question 17

LOD score greater than 3 indicates?

Answer 17

The two loci are linked and are close to one another (will inherit genes and can track disorder)

Question 18

Thrifty Phenotype Hypothesis

Answer 18

An adaptation that maximizes the chance of surviving in an adverse environment with limited caloric intake

Question 19

Thrifty Phenotype and Premature birth (low birthweight)

Answer 19

nutrient restriction in utero for baby, results in adjusted metabolism, but after birth the exposure to normal levels of nutrient can result in development of complex diseases (HTN, Stroke, Diabetes)

Question 20

Phenocopies

Answer 20

Phenotypes that are the same as the disease but different genotype to disease

Question 21

Genome Wide Association Studies (GWAS)

Answer 21

Involves rapidly scanning markers (SNPS) across the complete sets of DNA or genomes of many people to find genetic variations associated with a particular disease

Question 22

why do we use GWAS?

Answer 22

to find genetic variations to common complex diseases (asthma, cancer, diabetes, heart disease, mental illnesses

Question 23

Case and Control Studies

Answer 23

look retrospectively at what the patient was exposed to (subjected to all kinds of bias)

Question 24

Prospective Cohort Studies

Answer 24

Identify a cohort and follow group into future (best study and most accurate)

Question 25

Disadvantages of Prospective Cohort study

Answer 25

- Study might be too long - loss of participants - inconsistent meet and check in - disappointing results