ABSTRACT
Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication. To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data. Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity.
Subject(s)
Animals, Domestic/genetics , Dogs/genetics , Genome/genetics , Haplotypes/genetics , Polymorphism, Single Nucleotide/genetics , Animals , Animals, Domestic/classification , Animals, Wild/classification , Animals, Wild/genetics , Breeding , Computational Biology , Dogs/classification , Evolution, Molecular , Asia, Eastern/ethnology , Middle East/ethnology , Phenotype , Phylogeny , Wolves/classification , Wolves/geneticsABSTRACT
The number of annotated protein coding genes in the genome of Caenorhabditis elegans is similar to that of other animals, but the extent of its non-protein-coding transcriptome remains unknown. Expression profiling on whole-genome tiling microarrays applied to a mixed-stage C. elegans population verified the expression of 71% of all annotated exons. Only a small fraction (11%) of the polyadenylated transcription is non-annotated and appears to consist of approximately 3200 missed or alternative exons and 7800 small transcripts of unknown function (TUFs). Almost half (44%) of the detected transcriptional output is non-polyadenylated and probably not protein coding, and of this, 70% overlaps the boundaries of protein-coding genes in a complex manner. Specific analysis of small non-polyadenylated transcripts verified 97% of all annotated small ncRNAs and suggested that the transcriptome contains approximately 1200 small (<500 nt) unannotated noncoding loci. After combining overlapping transcripts, we estimate that at least 70% of the total C. elegans genome is transcribed.
Subject(s)
Caenorhabditis elegans/genetics , Chromosome Mapping/methods , Oligonucleotide Array Sequence Analysis/methods , Animals , Caenorhabditis elegans Proteins/genetics , Exons , Gene Expression Profiling , Genome, Helminth , Genomics , RNA, Helminth/genetics , RNA, Untranslated/genetics , Transcription, GeneticABSTRACT
This study explores the roles of genome copy number abnormalities (CNAs) in breast cancer pathophysiology by identifying associations between recurrent CNAs, gene expression, and clinical outcome in a set of aggressively treated early-stage breast tumors. It shows that the recurrent CNAs differ between tumor subtypes defined by expression pattern and that stratification of patients according to outcome can be improved by measuring both expression and copy number, especially high-level amplification. Sixty-six genes deregulated by the high-level amplifications are potential therapeutic targets. Nine of these (FGFR1, IKBKB, ERBB2, PROCC, ADAM9, FNTA, ACACA, PNMT, and NR1D1) are considered druggable. Low-level CNAs appear to contribute to cancer progression by altering RNA and cellular metabolism.
Subject(s)
Breast Neoplasms/genetics , Genomics , Transcription, Genetic , Breast Neoplasms/etiology , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Chromosome Aberrations , Female , Gene Amplification , Gene Dosage , Gene Expression Profiling , HumansABSTRACT
A high-throughput GeneChip® probe array platform was established. This system offers automated processing of 96 samples in the industry standard 96-well plate format. We demonstrate that this new technology can deliver the same performance as the standard cartridge probe arrays.