Further Mapping and Human Haplotypes Flashcards
(10 cards)
What is a haplotype?
a group of alleles in an organism that are inherited together from a single parent, often discussed in the context of tightly linked Single Nucleotide Polymorphisms
(SNPs).
What is a karyotype?
An organisms full set of chromosomes
What is the function of telomeres?
Telomeres, like the crimps on the end of laces, protect the ends of the chromosomes from degradation. With every division, the repetitive sequence that makes them up gets shorter, imposing the Hayflick limit. Problems with telomerase and regulation of this degradation cause cancer.
How are haplotypes used to map the genome?
If many individuals have a certain (previously genotyped) tag SNP of known location on the genome and also have a certain trait/gene (linkage disequilibrium), it can be inferred that this gene is in the same haplotype and region of the genome.
How does a Genome Wide Association Study work?
2 groups, one with a specific trait e.g. schizophrenia, and another control. Both groups analysed for 10^3 to 10^6 SNPs genome wide, and frequency of alleles is compared between groups to see if any are associated with the trait (very stringent p values). Follow up studies e.g. sequencing, fine mapping, are used to identify the gene itself, as SNPs in association might just be in linkage disequilibrium.
Describe a Manhattan plot
X-axis - SNP location in Chromosome order. Y-axis - Probability of association with a trait. Peaks of the skyline correspond to probable regions of association. Can be used for traits like schizophrenia, type-2 diabetes or even continuous traits like height (less success).
Describe the sickle cell haplotypes
All individuals have the same mutation, but individuals vary in the combination of SNPs around the mutation. There are 5 different haplotypes, implying 5 different origins of the mutations; Benin Cameroon, Central African Republic, Saudi Arabia, India and Senegal. Convergent evolution due to malaria selection pressure.
How did DDT create a house-fly haplotype?
Use of the insecticide from the 40s to combat insect-borne diseases imposed selection for a resistant haplotype that quickly spread through the global population of house-flies, causing a selective sweep in the haplotype in which the mutation was found.
What are the selection pressures involved in skin colour evolution?
High UV - causes cancer and folic acid degradation, causing spina bifida and other neural tube defects in pregnancies - pressure for more UV-absorbing melanin and darker skin. Low UV - vitamin D produced in response to absorption, impaired if skin is too dark for the environment. Deficiency causes rickets, infections, lung disease, autoimmune diseases, cancers, mental disorders etc.
What is the best-studied gene involved in global skin pigmentation?
SLC24A5 first discovered in zebrafish. In humans it is associated with two different SNP variants A/G found across the world. The A variant more common in Europe associated with white skin, the ancestral G variant common in Africa associated with dark skin. The darker skin allele is also found in Asian populations, but their skin colour is modified in other ways.
