Genes Lecture 6-Human genetics

Question 1

Why Identifying Disease Genes Matters?

Answer 1

1. Genetic Testing for Disease Prevention
2. New Treatments
3. Insight into Common Diseases

Question 2

steps to identify the genes from a disease

Answer 2

1. pedigree analysis: identify the occurrence of the disease in families
2. linkage analysis: evidence of genetic linkage and genetic markers to map the gene as precisely as possible
3. positional cloning of the disease gene: select candidate genes in the region of the chromosome and look for disease-associated mutations in each candidate gene

Question 3

dominant vs recessive diseases in a pedigree tree

Answer 3

Dominant- will see a diseased individual in every gen of family tree as only one allele needs to be present in genome
Recessive- skipping of generations due to the need of two alleles ; parents are likely to be carriers of specific disease (heterozygous carriers)

Question 4

X-linked diseases in a pedigree tree

Answer 4

If it was an x linked inheritance sons will have inherited recessive alleles from the mother (no father to son transmission)

Question 5

why do pedigree trees have complications

Answer 5

-incomplete penetrance or variable expressivity
-delayed onset e.g. breast cancer or Huntington
-genetic heterogeneity: mutations in different genes give the same disease
e.g. at least three genes are known to cause familial early-onset Alzheimer’s disease
look at more ‘genetically homogeneous’ populations e.g. Icelanders, Mormons
-non paternity/misattributed paternity

Question 6

features of DNA markers

Answer 6

polymorphic i.e. there must be two (or more) alleles present in a significant proportion of the population

easy to assay i.e. it must be easy to distinguish accurately one allele from another

Question 7

common DNA markers used

Answer 7

Commonly used DNA markers
1. Short tandem repeats (STRs)
2. Single nucleotide polymorphisms (SNPs)

Question 8

STRs

Answer 8

microsatellite repeats are tandem repeats of a short sequence, usually 2-4 nucleotides, and usually in non-coding sequences
Longer repeats (>10 nucleotides) are known as minisatellite repeats
*individuals differ with the number of repeats present in their genome

Question 9

Forensic analysis using STRs

Answer 9

use PCR and gel electrophoresis
-Crime Scene Evidence: DNA from hair, blood, saliva, or semen can place someone at a crime scene
-Family Links: A partial DNA match can suggest a close relative of the individual is in the database.

Question 10

SNPs

Answer 10

A single nucleotide difference between individuals
Most SNPs are in non-coding DNA
The most common type of polymorphism in human genome (~10 million common SNPs, one every 300 bp)
*Human genomes are 99.9% similar and majority of difference is coming from single nucleotide polymorphisms (0.1% )

Question 11

Principle of linkage analysis with SNPs

Answer 11

markers that identify the mutation must be present over many generations

Question 12

what can be used to genotype SNPs

Answer 12

GeneChip
Each SNP is tested for linkage with the disease phenotype using the appropriate genetic model

Question 13

positional cloning

Answer 13

Identify candidate genes by inspection of the human genome sequence in that region
Sequencing of the candidate genes in affected and unaffected individuals

Question 14

Disease gene discovery with Next Generation Sequencing (NGS)

Answer 14

Sequence affected and unaffected individuals.
Identify rare variants shared by only affected individuals.
Focus on candidate genes for potentially causative variants.
Study the functional impact of these variants.
Effective for identifying new mutations in parent-child trios.