A survey of genetic and epigenetic variation affecting human gene expression Export

@article{pastinen:2004, abstract = {The identification of human sequence polymorphisms that regulate gene expression is key to understanding human genetic diseases. We report a survey of human genes that demonstrate allelic differences in gene expression, reflecting the presence of putative allele-specific cis-acting factors of either genetic or epigenetic nature. The expression of allelic transcripts in heterozygous samples is assessed directly by relative quantitation of intragenic marker alleles in messenger or heteronuclear RNA derived from cells or tissues. This survey used 193 single-nucleotide polymorphisms (SNPs) from 129 genes expressed in lymphoblastoid cell lines, to identify 23 genes (18\%) with common allele-specific transcripts whose expression deviated from the expected equimolar ratio. A subset of these deviations, or "allelic imbalances," can be observed in multiple samples derived from reference CEPH ("Centre d'Etude du Polymorphisme Humain") pedigrees and demonstrate a spectrum of patterns of transmission, including cosegregation of allelic skewing across generations compatible with Mendelian inheritance as well as random monoallelic expression for three genes (IL1A, HTR2A, and FGB). Additional studies for BTN3A2 provide evidence of SNPs and haplotypes in complete linkage disequilibrium with high- and low-expressing transcripts. The pipeline described herein offers tools for efficient identification and characterization of allelic expression allowing identification of regulatory sequence variants as well as epigenetic variation affecting human gene expression. 10.1152/physiolgenomics.00163.2003}, author = {Pastinen, Tomi and Sladek, Robert and Gurd, Scott and Sammak, Alya'a and Ge, Bing and Lepage, Pierre and Lavergne, Karine and Villeneuve, Amelie and Gaudin, Tiffany and Brandstrom, Helena and Beck, Allon and Verner, Andrei and Kingsley, Jade and Harmsen, Eef and Labuda, Damian and Morgan, Kenneth and Vohl, Marie-Claude and Naumova, Anna K. and Sinnett, Daniel and Hudson, Thomas J.}, citeulike-article-id = {1610348}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/physiolgenomics.00163.2003}, citeulike-linkout-1 = {http://physiolgenomics.physiology.org/cgi/content/abstract/16/2/184}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/14583597}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=14583597}, day = {15}, doi = {10.1152/physiolgenomics.00163.2003}, journal = {Physiol. Genomics}, month = {January}, number = {2}, pages = {184--193}, posted-at = {2007-09-28 16:18:57}, priority = {2}, title = {A survey of genetic and epigenetic variation affecting human gene expression}, url = {http://dx.doi.org/10.1152/physiolgenomics.00163.2003}, volume = {16}, year = {2004} }

TY - JOUR ID - pastinen:2004 L3 - citeulike-article-id:1610348 N2 - The identification of human sequence polymorphisms that regulate gene expression is key to understanding human genetic diseases. We report a survey of human genes that demonstrate allelic differences in gene expression, reflecting the presence of putative allele-specific cis-acting factors of either genetic or epigenetic nature. The expression of allelic transcripts in heterozygous samples is assessed directly by relative quantitation of intragenic marker alleles in messenger or heteronuclear RNA derived from cells or tissues. This survey used 193 single-nucleotide polymorphisms (SNPs) from 129 genes expressed in lymphoblastoid cell lines, to identify 23 genes (18%) with common allele-specific transcripts whose expression deviated from the expected equimolar ratio. A subset of these deviations, or "allelic imbalances," can be observed in multiple samples derived from reference CEPH ("Centre d'Etude du Polymorphisme Humain") pedigrees and demonstrate a spectrum of patterns of transmission, including cosegregation of allelic skewing across generations compatible with Mendelian inheritance as well as random monoallelic expression for three genes (IL1A, HTR2A, and FGB). Additional studies for BTN3A2 provide evidence of SNPs and haplotypes in complete linkage disequilibrium with high- and low-expressing transcripts. The pipeline described herein offers tools for efficient identification and characterization of allelic expression allowing identification of regulatory sequence variants as well as epigenetic variation affecting human gene expression. 10.1152/physiolgenomics.00163.2003 IS - 2 JF - Physiol. Genomics EP - 193 TI - A survey of genetic and epigenetic variation affecting human gene expression VL - 16 SP - 184 AU - Pastinen, Tomi AU - Sladek, Robert AU - Gurd, Scott AU - Sammak, Alya'a AU - Ge, Bing AU - Lepage, Pierre AU - Lavergne, Karine AU - Villeneuve, Amelie AU - Gaudin, Tiffany AU - Brandstrom, Helena AU - Beck, Allon AU - Verner, Andrei AU - Kingsley, Jade AU - Harmsen, Eef AU - Labuda, Damian AU - Morgan, Kenneth AU - Vohl, Marie-Claude AU - Naumova, Anna AU - Sinnett, Daniel AU - Hudson, Thomas PY - 2004/01/15/ UR - http://dx.doi.org/10.1152/physiolgenomics.00163.2003 ER -