22 terms

Human Genome Project

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What is the goal of linkage analysis?
-to identify a region that is inherited in affected progeny but not in unaffected progeny.
What were the goals of the human genome project?
-create genetic and physical maps of all chromosomes.
-determine the sequence of 3 billion base pairs of DNA in the genome.
-identify the entire set of genes in the genome.
What were the goals of the human genome project?
-analyze genetic variations among humans (SNPs).
-map and sequence the genomes of model organisms (yeast, fruit flies, mice, etc.).
-examine ethical, social, and legal issues.
What is the total number of genes?
25,000
What is the smallest chromosome?
-Chromosome 21
Which chromosome has the smallest number of genes?
Y chromosome
About how many percent of the human genome do exons make up?
about 1.5%
About how many percent of the human genome do introns make up?
about 25%
How many different proteins are made by human cells?
100,000 - 150,000
What is the correlation between genome size and species complexity?
There is no correlation. Humans also do not have the largest genome.
What is synteny?
-The condition of two or more genes being located on the same chromosome whether or not there is demonstrable linkage between them (i.e., region 2 in mouse chromosome 1 vs. human chromosome 2).
How often do variations occur in the genome?
-1 per 100 base pairs
How many SNPs occur on the DNA level between 2 individuals? How many differences?
-1 SNP per 1000 base pairs.
-3 million differences between individuals
What is the SNP frequency in populations?
- greater than 90 percent of SNPs are observed in all populations.
-less than 10 percent of SNPs are population specific.
What is the goal of the 1000 Genomes Project? What did it find?
-Goal was to identify all common variants in the human population.
-over 41 million variants were identified after sequencing over 1000 individuals.
What is the SNP allele frequency?
18 million SNPs are present in >1% of the population (1 in every 162 bp)
Why is it sometimes difficult to identify causative genes using traditional linkage analysis?
-Late onset disease--difficult to obtain multiple generations.
-incomplete penetrance
-progression of disease is very rapid-difficult to obtain DNA samples.
-results in numerous genomic regions which are too large to sequence.
What is a novel approach to overcome the obstacles faced by traditional linkage analysis?
-exome sequencing (sequencing all exons in the genome).
-exome capture followed by next-generation sequencing.
Describe the exome sequencing approach.
-pick one or more family members.
-perform exome capture/deep sequencing
-identify variants in each sample
-filter variants based on several criteria
-identify causative mutation
Describe the filtering criteria in identifying causal mutation.
-is the variant present in both sequenced samples?
-is the variant observed in any SNP databases (1000Genomes or dbSNP)?
-is the variant a non-synonymous change?
-is the variant heterozygous (dominant trait)?
-does the variant map to a linkage peak?
What is the overall massive benefit of exome sequencing?
-Using 2 samples, you can go from 282,782 variants down to 2.
What are some ways in which personal genomes can be used in the clinic?
-routine diagnostic
-early identification of rare disorders
-risk of complex diseases
-tumor sequencing
-pharmacogenetics
-preventive medicine
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