Understanding Alleles, Population Genetics, and Ancestry in Gene Studies - Prof. Mihai Pop, Study notes of Computer Science

Download Understanding Alleles, Population Genetics, and Ancestry in Gene Studies - Prof. Mihai Pop and more Study notes Computer Science in PDF only on Docsity! CMSC423: Bioinformatic Algorithms, Databases and Tools Lecture 16 Genetics Reading assignment ● Chapter 13 CMSC423 Fall 2008 5 More definitions ● Genotype A/A is called homozygous (both chromosomes have the same allele) ● Genotype A/B is called heterozygous (mother and father's chromosomes disagree) ● Notes: ● phenotypes not necessarily directly correlated with a single gene – polygenic traits ● probability gene correlates with a phenotype – penetrance ● link between genotype and phenotype can be qualitative (gene “form” matters) or quantitative (gene dosage matters) CMSC423 Fall 2008 6 Technology – what we measure? ● Definition of allele/genotype depends on what we can measure – constantly changing ● We are looking for things that differ within a population – polymorphic markers: ● Restriction fragment length polymorphism (RFLP)– measures presence/absence of particular sites in the genome ● Variable number tandem repeats (VNTR) – specific repeat elements that occur in different copy numbers ● Single-nucleotide polymorphisms (SNPs) – single letter differences between chromosomes (>500,000 characterized) ● Copy number variants (CNV) – genomic regions whose copy number differs between individuals CMSC423 Fall 2008 7 Allele frequencies ● Population genetics questions: ● what alleles exist in a certain population? ● what is the relative abundance of the alleles? ● how “diverse” is a population? ● Given a locus (gene or genomic region), assume there are K possible alleles in a population and allele j occurs with frequency p j ● How “uniform” is the locus in the population? Likelihood two random individuals have same allele homzygosity F=∑i=1 K pi 2 CMSC423 Fall 2008 10 Who am I? ● Inferring ancestry as described is overly-simplistic ● Can do more fancy statistics ● However: any statistical approach is error prone – answer is associated with level of confidence, i.e. probability answer is wrong (remember P-values?) ● Beware of anyone who claims to infer your ancestry from genotype ● Beware of anyone who claims to infer disease susceptibility from genotype - need genetic/risk counselors not companies providing information for “entertainment purposes” CMSC423 Fall 2008 11 Recombination ● Genetic change not only caused by mutations ● Recombination – DNA “jumps” between homologous chromosomes due to cross-over events A1 B1 C1 D1 A1 B1 C1 D1 A2 B2 C2 D2 A2 B2 C2 D2 A1 B1 C2 D2 A2 B2 C1 D1 A1 B1 C2 D1 A2 B2 C1 D2 CMSC423 Fall 2008 12 Association studies ● The set of alleles on a same chromosome – haplotype ● If a particular allele of a gene is always associated with a phenotype (disease) – is this gene causing the disease? ● Most likely – gene is associated/nearby with the gene causing the disease (their alleles always appear on the same haplotype) ● Due to recombination a set of original haplotypes rapidly becomes broken apart ● How likely is it that two alleles remain on the same haplotype (are linked) during evolution? CMSC423 Fall 2008 15 Additional resources ● www.hapmap.org ● www.1000genomes.org ● www.personalgenomes.org ● http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim CMSC423 Fall 2008 16 Homework ● Prove the equalities on slide 13 (D = ...) ● Derive the formula for Dmax on slide 14 (problem 3.5 in book) ● Due Tuesday Nov 4 – submit by E-mail to me and Mohammad