Further Mapping and Human Halotypes - 08

what is a halotype?

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 was the aim of the International HapMap Project?

aimed to locate about 3 million human SNPs, we have identified about 10 million SNPs in the human genome.

what is the Genome wide association study (GWAS)?

• uses many different genomes from 2 different groups of individuals.

• the first group share a particular trait, the second is a control group.

• if a particular locus is associated with the phenotype of interest, individuals who share the trait will share the same genetic variant.

• GWAS tests the association to SNPs, produce outputs called Manhattan Plots

  • on the x axis - SNO location in chromosome order

  • on the y axis - the probability the SNP is associated with the trait of interest

  • ‘peaks’ correspond to regions of association

what has GWAS been used to map?

• variants associated to human diseases such as systemic lupus erythomatosus, schizophrenia and type-2 diabetes.

  • can also be used to study the location of loci associated with continuous traits such as height

what is the genome project?

in 2018, Genomics England completed the 100,000 Genome Project

• mostly people NHS patients with rare diseases such as cancers and their families

  • will improve our understanding of the genetics of these diseases

• NHS is now running the 5 million genome project

what are sickle cell halotypes?

• all individuals have the same mutation, but individuals vary in the combination of SNPs around the mutation

• there are 5 different halotypes, implying 5 different origins of the mutations: Benin Cameroon, Central African Republic, Saudi Arabia, India and Senegal

where did the sickle cell mutation likely come from?

• likely arose due to natural selection as it gave resistance to malaria.

• the 5 halotypes have likely evolved independently

• Portugal being a former empire has many of these halotypes in its population, shows the significance of migration on allele frequencies

• house flies - used to be controlled with pesticides DDT, a halotype arose which gave resistance to this, a selective sweep selected for this halotype and is now present all around the world.

what are halotypes for human skin colour?

• colour pigment - melanin and the amount of melanin produced in different populations has been selected for

• natural selection has driven a gradient of dark colour skin near the equator, and lighter colour skin at more extreme latitudes

  • darker skin arise in humans as protection from UV radiation, protect against skin cancers, folic acid strongly absorbs UV & decreases in concentration

  • lighter skinned pregnant women more likely to have offspring with spina bifida in high UV environments

why was darker pigment lost in more extreme latitudes?

• unable to make vitamin D

• this is produced when the skin absorbs UV, but individuals with darker skin cannot absorb enough UV

describe vitamin D deficiency

• Vitamin D deficiency commonly associated with rickets - highest incidence in darker skin individuals

• also associated with increases in infections, lung disease, autoimmune disease, cancers, mental disorders

  • Scotland historically had the highest level of rickets in the UK

what alleles are selected for skin colour?

• 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