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Thursday, February 25, 2010

AGBT 2010 - Michael Zody - Broad

Detecting signatures of selection in domestic chickens by whole genome re-sequencing

Work Mostly done at Upsalla university

Chickens were domesticated ~8000 chicken.
Mainly descended from red jungle fowl

Sequence pools of chickens - what are most variant alleles?
Used SOLiD sequencing - 4-5x coverage for each chicken

Model organisms... this is a different type of model.
Question: Can we find the loci that underly variations that people have selected for in domestication

Why use chickens?
* numerous QTL
*small genome
* etc

Draft chicken genome already
* 3 million snps (capilliary reseq)
* microsatelite and snp maps
* 38 autozome + W and Z
* 10 are macro rechromosomes
* 28 microchromosomes - high gc + recombination
* 9 of them have no sequences yet in draft.

Genome is 1Gb
* Female has WZ, male has ZZ.
* W is poor.

Two libraries of red jungle fowl.
* one from a pool of 8 from a zoo
* second was the reference genome.

Also did some commercial chickens (broiliers?)
high growth and low growth from *white plymouth rock", selected for high and low growth.
high growth chicken has a huge appetite - will eat themselves to death
low growth chickens are anorexic.. won't reproduce at all if not required to eat.
Other strains:
* rhode island.,
* white leghorns

[Wow... lots of types of chickens.. I'm taking more on this part]

80% of genome covered in ref.
7Million snps identified - corrona lite caller
Most of snps are high quality - tested with arrays, and get 98.8% validation
Some errors seen are in reference chicken

saw some evidence of grey jungle fowl in the domestic bird. (Yellow skin....)

Selective sweeps
* looking for regions of homozygosity.
* use Z score -6
* proof of principe: BCDO2, yellow skin
* graph showing windows of heterozygosity - drops dramatically around BCDO2
* demonstrate power to do sweeps.

Can do this over the whole genome.
* 23 loci in "all domestic" had one or more windows ZH < -6
* 9 loci in boilers only, 6 in layers only.
* TSHR - early domesticaion locus in chickens?

Key step in domestication of chicken was the lack of seasonal reproduction check
* Look for this in genomes.

Also look for deleterious mutation
* eg, myostatin mutation in double-muscled cattle
* Loss of function may be positively selected
* may accumulate due to relaxed restrictions

look for gene mutations, fixed in one or more line
* remember, using pooled data

* removed anything not covered in reference
* calulate p-value
correct for multiple
only considered autosomes
dletions matched to Ensemble

1,284 mutations
* 27 in protein coding regions by annotation
* only 7 of them were real deletions
* validate by sanger

Known deletion (GHR)
* turned out to be a good control.
* detected as 1802bp deletion in commercial broiler 2
* removes c-terminous, modifies protein
* causes sex-linked dwarfism
* used to reduce growth.... interesting aside about how this deletion is used commercially

Novel deletion (SH3RF2)
* removes exons 2-5. (human)
* deletion in high-growth line
* possible problems in annotation
* found in QTL region

Phenotype-genotype correlation
* strongly associated with growth rate
* affects males and females
* Effect not linked to parent.
* Tested expression - doesn't change at exon 1
* No expression in exons 2-5 in high.
* This gene may play a role in appetite

May be a great model for future work on other domesticated model organisms.



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