L8 - Further mapping and human haplotypes

What is a Hapolotype

A group of alleles in an organism that are inherited together from a single parent

What are telomeres

• Are sequences on the ends of chromosomes - stop chromosome form wearing way

• every time that chromosome divides looses a bit of the sequence

• when gets to a critical level send signal to stop diving by telomere enzymes

• when goes wrong often causes cancer

is centromere always in teh middle

no

• can be Metacentric,

  acrocentric, telocentric

Chromosmes in drosophila

• have polytene chromomes which are very large found in certain cells

• e.g. salivary galnds

First case of seeing gene regulation

• If give heat shock to drosophila

• see polytene chromosomes produce something called chaperonases

• these go and wrap themselves around protein to protect them form damage

• expressed more regularly then think

• these are found in cancer cells, can be a good indicator of someone is going to get cancer

Other ways we can map chromosomes:

FISH

Somatic cell hybridation

Radiation hybrid mapping

Fluorescent in-situ hybridisation

• physical way of identifying gene activity

• make a complementry DNA sequnce for the gene you are looking for

• Avadin label this with fluorescent dye

• float your DNA above genome and will attack to complementary sequence and will give a bright spot

• you are FISHing for genes

Somatic cell hybridization

• first cells to grow in culture were Hela cells, caused by cervical cancer immortalized as never stop growing - used in somatic cell genetics

• If join human and mouse cell in culture get something called Sendai virus - has attachment proteins on surface which make it stick together

• Surprisingly enough the cell membranes occasionally fuse to make a “somatic cell hybrid”

• This contains chromosomes from both species

• We can select the cells that have fused together by giving a poison that needs both an enzyme form mouse and human to break it down - any cells that have not fused will die

• The human chromosomes will then be spat out as they divide- can be seen under a microscope

Radiation hybrid mapping

• Desired chromosomes are broken down into segments with X-rays

• Then implanted into rodent cells which close chromosomes

• Loci which are far apart are more likely to be in different segment compared to loci which are close together

what do GWAS test

• test the association of SNIP’s

• see if people share a particular variant that causes a disease e.g. in Lupus, type 2 diabetes, schizophrenia

• produce Manhattan plots

Sickle cell haplotypes

• all have same mutaion but differ in the SNIPs surround the mutation

• 5 different haplotypes : Benine Camaroon, Central African republic, senegal, India and Saudi Arabia

• Sickle cell mutation came about due to natural selection as provides resistance against Malaria

• The 5 different haplotypes probably evolved individually

House flies

• used to kill them using DDT which is a pesticide

• but a haplotype arose which gave resistance to DDT

• lead to a selective sweep and now this haplotype is found in all house flies world wide

Haplotype for human skin color

• different amounts of melanin has been selected for in different populations

• In areas closer to equator have darker skin which protects them form UV and skin cancer, and helps maintain folic acid (which is destroyed by UV) - stops spine abifida

• in areas at high altitude - lighter people evolved to absorb vitamin D but people with darker skin risk vitamin D deficiency and so risk poroblems like rickets, infections, lung disease, autoimmune diseases, cancers, and mental disorders

• Scotland has highest level of rickets in UK

• many alleles are selected for skin color in Humans have 2 SNIPs A and G. A found in Europe light skin

• G found in Africa darker skin

• Asia had G variant but modified in different way