DNA and Genotyping methods Flashcards
DNA organisation
23 chromosomes in humans. Each CSM contains single long molecule of DNA, wrapped up in proteins (histones) = Cromatin super coiled into chromatids.
DNA organisation
23 chromosomes in humans. Each CSM contains single long molecule of DNA, wrapped up in proteins (histones) = Cromatin super coiled into chromatids.
Sugar and phosphate attached to each nucleotide - Adenin, Guanine, Thyin and Cytosine.
3 billion nucleotides in genome.
Genes
there are non-coding regions of DNA.
Genotyping
Processing of determining sequences of DNA and how that changes a phenotype.
Identify pathogens and mutations in bacterias. Paternity tests. Forensic science.
Genetic variatiion
Variation in the DNA sequence - mutations and polymorphisms.
Genetic variation causes - origins
Mutation = Problem in cell division and replication. Recombination changes.
Natural selection.
Genetic variation causes - origins
Mutation = Problem in cell division and replication. Recombination changes.
Natural selection.
Population size - genetic drift (changes in diversity), bottleneck and founder effect.
Genetic variation causes - origins
Mutation = Problem in cell division and replication. Recombination changes.
Natural selection.
Population size - genetic drift (changes in diversity), bottleneck and founder effect.
Gene flow - migration. Mix allels of DNA and increase variability.
Sexual reproduction - gene combination.
Genetic variatiion
Variation in the DNA sequence - mutations and polymorphisms.
Can trace back mutations by looking at DNA and would increase in occurrence over time. Can check how old mutation is.
Mutations and polymorphisms
A point or change in a section of DNA that varies between individuals.
Can directly influence traits/cause diseases.
Located in coding and non-coding DNA.
PM >1% population.
Mutation very rare. less than 1% of pop.
Somatic genetic mutations
Sun bathing. Over time you have changes to your DNA. Not passed through generations - Lung and skin cancer.
Germline mutations
Inherited from parent to child from Gametes into embryo.
Some types of cancer and present throughout life.
De Novo
Not inherited - occur after fertilisation. Can be passed on. Some forms of cancer
Genetic polymorphisms
- Sequence repeats
- Copy number variants
- Positional variants
- Single Nucleotide Polymorphisms (SNPs).
Sequence repeats
Small segments of DNA repeated. Variable tandem repeats (VTR).
Minisatalites (10-50bp repeats)
Microsatalites (shorter than 0.1 kb)
Sequence repeats (genetic polymorphism)
Small segments of DNA repeated. Variable tandem repeats (VTR).
Minisatalites (10-50bp repeats)
Microsatalites (shorter than 0.1 kb)
Example of Sequence repeats - M = Huntington’s Disease
Repeats of CAG.
Increased number of repeats and depending where they are is can change course of disease. more than 40 copies = more severe.
Atrophy of basal ganglia.
Copy number variants (CNV - genetic polymorphisms)
Changes from 1 kb TO SEVERAL MEGA BASES. Structural variation - abnormal nuber of copies in one of more sections of genome.
Can encompass entire genes including important regulatory elements.
Accounts for 12% human genomic DNA.. Can be inherited or de novo. Associsated with susceptibility or resistance of disease.
Example = autism or schizophrenia.
Poly variants (genetic polymorphisms)
Inversion - Breakage during miosis where changes order of DNA. Gtes inverted and can make gene faulty.
Translocation - Breakage of DNA from two different chromosomes that can swap.
Example - downsyndrome. -
Single Nucleotide Polymorphisms (genetic polymorphism)
1 SNP in every 300 bases - 10M. TT (homozygous) TG/GT (heterozygous) GG (homozygous) Silent (No amino acid change) Missense (replacement of one amino acid) Nonsense (premature stop codon)
Linkage Disequilibrium
Non-random association of alleles at two or more loci - individuals who have one allele tend to have the second allele as well.
Linkage Disequilibrium
Non-random association of alleles at two or more loci - individuals who have one allele tend to have the second allele as well.
Always go close to each other.
Haplotyope blocks
In genome recombination happening all the time. different areas different amounts of recombination.
Haplotype blocks are a set of closely linked alleles on a chromosome that tend to be inherited togethr over time.
High level of recomb = many HAP blocks and low Linkage disequilibrium.
Low level of recombination = few HAP blocks and high linkage disequilibrium.
How do we but linkage disequilibrium in genotyping?
Tag SNPs.
I DONT GET THIS.
Capture variation across a whole gene using a limited number of SNPs by identifying blocks of DNA that co-segregate (HAP blocks).
