Systematic Inference of Copy-Number Genotypes from Personal Genome Sequencing Data Reveals Extensive Olfactory Receptor Gene Content Diversity

Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95–99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ∼15% and ∼20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high-throughput sequencing

Additional file 7: Table S9. of The human olfactory transcriptome

Genes that are discussed in the text. (XLSX 37 kb

Sciaphila japonica Makino

原著和名: ホンガウサウ科名: ホンゴウソウ科 = Triuridaceae採集地: 高知県 土佐清水市 (土佐 土佐清水市)採集日: 1978/8/19採集者: 萩庭丈壽整理番号: JH009346国立科学博物館整理番号: TNS-VS-95934

Additional file 2: Table S2. of The human olfactory transcriptome

Whole genome expression of the studied samples (in FPKM). FC_OE, the fold change of the human olfactory epithelium relative to the controls; FC_resp, the fold change of the human respiratory epithelium relative to the controls; FC_MOE, the fold change of mouse olfactory epithelium relative to the controls, FC_MOB, the fold change of mouse olfactory bulb relative to the controls. NoOrth- no mouse ortholog. OSN- olfactory sensory neurons in RPM (reads per million). (XLSX 22311 kb

Additional file 5: Table S7. of The human olfactory transcriptome

Expression profile of the OR repertoire. (XLSX 161 kb

Additional file 4: Table S6. of The human olfactory transcriptome

Expression of the lipocalin family members. Mouse was calculated relative to Mouse ENCODE data ( http://chromosome.sdsc.edu/mouse/download.html ), see methods. (XLSX 14 kb