Chapter 6 Lec 4 Flashcards
Discuss the challenges and opportunities of the dog genome.
1) it belongs to an outgroup of Euarchontoglires, mammalian group that includes humans.
2) they are ideal species for studying domestication; offer inbred populations (as well as different breeds) and wild populations.
3) it’s genome and the wolves are much closer than human vs chimpanzee; seq divergence of the canids is 0.04% in exons and 0.21% in introns(thus, 4 and 21 differences per 100 bp, respectively); in addition, they can still mate with each other.
4) they share many diseases with humans; yet ,many diseases are specific individual breeds and genealogical + clinical records are available; most breeds are highly inbred, leading to small founder populations and even bottlenecks- simplifies the search for disease-causing genes/ mutations
5) dogs are at times used for drug testing and gene therapy research, thus, it’s ideal to understand their molecular biology.
6) they show vast morphological variation(e.g. size) - making genetic regulation of development an important feature of comparative genomics in canids; in fact, a single mutation is now known to control skull breadth and short face (similarly, a single mutation explains the great Dane vs chihuahua)
7) differences in dog personality traits- opportunity to study genes associating with behavior.
Discuss the history of dog.
1) the order Carnivora originated ~60 MYA; current closely- related species (e.g. wolf, coyote, jackal,fox) branched off 3-4 MYA , with wolf lineage giving rise to domesticated dog.
2) archaeological evidence indicates that domestication took place over the last 20000 years.
3) there is also evidence that dogs underwent two populations bottlenecks; thus, ~9000 generations ago(or ~27000yrs) and recently ~30-90 generations ago(coincides with the beginning of breed divergence; it is currently estimated that there are as many as 1000 different breeds.
Discuss the genome variation among breeds of dogs.
1) first genome to be sequenced was female ‘boxer’(named Tasha); used WGS method (shotgun method)
2) the dog genome is slightly smaller than humans due to fewer repeats.
3) in addition to generating reference dog genome, 2.5 million SNPs were uncovered from 11 breeds; few SNPs occurred within breeds than between breeds; for e.g. there is ~1 SNP per 1600bp in boxer’s, but ~1SNP per 900bp between breeds.
Briefly explain the consequences of closer relationships within breeds.
1) greater interbreed than intrabreed seq differences.
2) longer haplotypes blocks- up to 100kb (within breeds) and 10kb(between breeds)
3) Linkage disequilibrium (LD) within breeds extend over several Mbp- across breeds it is greatly reduced, extending only over 10’s of kb’s.
Provide with comparison of dog, human and mouse genomes.
1) Dogs have 39 pairs of chromosomes vs 23 and 21 in humans and mice, respectively; yet, 94% of dog genome is in synteny with human and mouse genomes.
2) ~5% of dog genome has functional elements that it shares with humans and mice; included in the functional elements is regulatory elements as well as non-protein-coding RNAs - thus, one should never dismiss as ‘junk’ areas for which functions remain unknown.
