RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting

Bharati Jadhav, Ramin Monajemi, Kristina K Gagalova, Daniel Ho, Harmen H M Draisma, Mark A van de Wiel, Lude Franke, Bastiaan T Heijmans, Joyce van Meurs, Rick Jansen, Peter A C 't Hoen, Andrew J Sharp, Szymon M Kiełbasa, GoNL Consortium

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Identification of imprinted genes, demonstrating a consistent preference towards the paternal or maternal allelic expression, is important for the understanding of gene expression regulation during embryonic development and of the molecular basis of developmental disorders with a parent-of-origin effect. Combining allelic analysis of RNA-Seq data with phased genotypes in family trios provides a powerful method to detect parent-of-origin biases in gene expression.

RESULTS: We report findings in 296 family trios from two large studies: 165 lymphoblastoid cell lines from the 1000 Genomes Project and 131 blood samples from the Genome of the Netherlands (GoNL) participants. Based on parental haplotypes, we identified > 2.8 million transcribed heterozygous SNVs phased for parental origin and developed a robust statistical framework for measuring allelic expression. We identified a total of 45 imprinted genes and one imprinted unannotated transcript, including multiple imprinted transcripts showing incomplete parental expression bias that was located adjacent to strongly imprinted genes. For example, PXDC1, a gene which lies adjacent to the paternally expressed gene FAM50B, shows a 2:1 paternal expression bias. Other imprinted genes had promoter regions that coincide with sites of parentally biased DNA methylation identified in the blood from uniparental disomy (UPD) samples, thus providing independent validation of our results. Using the stranded nature of the RNA-Seq data in lymphoblastoid cell lines, we identified multiple loci with overlapping sense/antisense transcripts, of which one is expressed paternally and the other maternally. Using a sliding window approach, we searched for imprinted expression across the entire genome, identifying a novel imprinted putative lncRNA in 13q21.2. Overall, we identified 7 transcripts showing parental bias in gene expression which were not reported in 4 other recent RNA-Seq studies of imprinting.

CONCLUSIONS: Our methods and data provide a robust and high-resolution map of imprinted gene expression in the human genome.

Original languageEnglish
Pages (from-to)50
JournalBiology
Volume17
Issue number1
DOIs
Publication statusPublished - 24 Jun 2019

Cite this

Jadhav, B., Monajemi, R., Gagalova, K. K., Ho, D., Draisma, H. H. M., van de Wiel, M. A., ... GoNL Consortium (2019). RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting. Biology, 17(1), 50. https://doi.org/10.1186/s12915-019-0674-0
Jadhav, Bharati ; Monajemi, Ramin ; Gagalova, Kristina K ; Ho, Daniel ; Draisma, Harmen H M ; van de Wiel, Mark A ; Franke, Lude ; Heijmans, Bastiaan T ; van Meurs, Joyce ; Jansen, Rick ; 't Hoen, Peter A C ; Sharp, Andrew J ; Kiełbasa, Szymon M ; GoNL Consortium. / RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting. In: Biology. 2019 ; Vol. 17, No. 1. pp. 50.
@article{0bb4ab2be3f44d5a88afda99b0fb638a,
title = "RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting",
abstract = "BACKGROUND: Identification of imprinted genes, demonstrating a consistent preference towards the paternal or maternal allelic expression, is important for the understanding of gene expression regulation during embryonic development and of the molecular basis of developmental disorders with a parent-of-origin effect. Combining allelic analysis of RNA-Seq data with phased genotypes in family trios provides a powerful method to detect parent-of-origin biases in gene expression.RESULTS: We report findings in 296 family trios from two large studies: 165 lymphoblastoid cell lines from the 1000 Genomes Project and 131 blood samples from the Genome of the Netherlands (GoNL) participants. Based on parental haplotypes, we identified > 2.8 million transcribed heterozygous SNVs phased for parental origin and developed a robust statistical framework for measuring allelic expression. We identified a total of 45 imprinted genes and one imprinted unannotated transcript, including multiple imprinted transcripts showing incomplete parental expression bias that was located adjacent to strongly imprinted genes. For example, PXDC1, a gene which lies adjacent to the paternally expressed gene FAM50B, shows a 2:1 paternal expression bias. Other imprinted genes had promoter regions that coincide with sites of parentally biased DNA methylation identified in the blood from uniparental disomy (UPD) samples, thus providing independent validation of our results. Using the stranded nature of the RNA-Seq data in lymphoblastoid cell lines, we identified multiple loci with overlapping sense/antisense transcripts, of which one is expressed paternally and the other maternally. Using a sliding window approach, we searched for imprinted expression across the entire genome, identifying a novel imprinted putative lncRNA in 13q21.2. Overall, we identified 7 transcripts showing parental bias in gene expression which were not reported in 4 other recent RNA-Seq studies of imprinting.CONCLUSIONS: Our methods and data provide a robust and high-resolution map of imprinted gene expression in the human genome.",
author = "Bharati Jadhav and Ramin Monajemi and Gagalova, {Kristina K} and Daniel Ho and Draisma, {Harmen H M} and {van de Wiel}, {Mark A} and Lude Franke and Heijmans, {Bastiaan T} and {van Meurs}, Joyce and Rick Jansen and {'t Hoen}, {Peter A C} and Sharp, {Andrew J} and Kiełbasa, {Szymon M} and {GoNL Consortium}",
year = "2019",
month = "6",
day = "24",
doi = "10.1186/s12915-019-0674-0",
language = "English",
volume = "17",
pages = "50",
journal = "Biology",
issn = "2079-7737",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",

}

Jadhav, B, Monajemi, R, Gagalova, KK, Ho, D, Draisma, HHM, van de Wiel, MA, Franke, L, Heijmans, BT, van Meurs, J, Jansen, R, 't Hoen, PAC, Sharp, AJ, Kiełbasa, SM & GoNL Consortium 2019, 'RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting' Biology, vol. 17, no. 1, pp. 50. https://doi.org/10.1186/s12915-019-0674-0

RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting. / Jadhav, Bharati; Monajemi, Ramin; Gagalova, Kristina K; Ho, Daniel; Draisma, Harmen H M; van de Wiel, Mark A; Franke, Lude; Heijmans, Bastiaan T; van Meurs, Joyce; Jansen, Rick; 't Hoen, Peter A C; Sharp, Andrew J; Kiełbasa, Szymon M; GoNL Consortium.

In: Biology, Vol. 17, No. 1, 24.06.2019, p. 50.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting

AU - Jadhav, Bharati

AU - Monajemi, Ramin

AU - Gagalova, Kristina K

AU - Ho, Daniel

AU - Draisma, Harmen H M

AU - van de Wiel, Mark A

AU - Franke, Lude

AU - Heijmans, Bastiaan T

AU - van Meurs, Joyce

AU - Jansen, Rick

AU - 't Hoen, Peter A C

AU - Sharp, Andrew J

AU - Kiełbasa, Szymon M

AU - GoNL Consortium

PY - 2019/6/24

Y1 - 2019/6/24

N2 - BACKGROUND: Identification of imprinted genes, demonstrating a consistent preference towards the paternal or maternal allelic expression, is important for the understanding of gene expression regulation during embryonic development and of the molecular basis of developmental disorders with a parent-of-origin effect. Combining allelic analysis of RNA-Seq data with phased genotypes in family trios provides a powerful method to detect parent-of-origin biases in gene expression.RESULTS: We report findings in 296 family trios from two large studies: 165 lymphoblastoid cell lines from the 1000 Genomes Project and 131 blood samples from the Genome of the Netherlands (GoNL) participants. Based on parental haplotypes, we identified > 2.8 million transcribed heterozygous SNVs phased for parental origin and developed a robust statistical framework for measuring allelic expression. We identified a total of 45 imprinted genes and one imprinted unannotated transcript, including multiple imprinted transcripts showing incomplete parental expression bias that was located adjacent to strongly imprinted genes. For example, PXDC1, a gene which lies adjacent to the paternally expressed gene FAM50B, shows a 2:1 paternal expression bias. Other imprinted genes had promoter regions that coincide with sites of parentally biased DNA methylation identified in the blood from uniparental disomy (UPD) samples, thus providing independent validation of our results. Using the stranded nature of the RNA-Seq data in lymphoblastoid cell lines, we identified multiple loci with overlapping sense/antisense transcripts, of which one is expressed paternally and the other maternally. Using a sliding window approach, we searched for imprinted expression across the entire genome, identifying a novel imprinted putative lncRNA in 13q21.2. Overall, we identified 7 transcripts showing parental bias in gene expression which were not reported in 4 other recent RNA-Seq studies of imprinting.CONCLUSIONS: Our methods and data provide a robust and high-resolution map of imprinted gene expression in the human genome.

AB - BACKGROUND: Identification of imprinted genes, demonstrating a consistent preference towards the paternal or maternal allelic expression, is important for the understanding of gene expression regulation during embryonic development and of the molecular basis of developmental disorders with a parent-of-origin effect. Combining allelic analysis of RNA-Seq data with phased genotypes in family trios provides a powerful method to detect parent-of-origin biases in gene expression.RESULTS: We report findings in 296 family trios from two large studies: 165 lymphoblastoid cell lines from the 1000 Genomes Project and 131 blood samples from the Genome of the Netherlands (GoNL) participants. Based on parental haplotypes, we identified > 2.8 million transcribed heterozygous SNVs phased for parental origin and developed a robust statistical framework for measuring allelic expression. We identified a total of 45 imprinted genes and one imprinted unannotated transcript, including multiple imprinted transcripts showing incomplete parental expression bias that was located adjacent to strongly imprinted genes. For example, PXDC1, a gene which lies adjacent to the paternally expressed gene FAM50B, shows a 2:1 paternal expression bias. Other imprinted genes had promoter regions that coincide with sites of parentally biased DNA methylation identified in the blood from uniparental disomy (UPD) samples, thus providing independent validation of our results. Using the stranded nature of the RNA-Seq data in lymphoblastoid cell lines, we identified multiple loci with overlapping sense/antisense transcripts, of which one is expressed paternally and the other maternally. Using a sliding window approach, we searched for imprinted expression across the entire genome, identifying a novel imprinted putative lncRNA in 13q21.2. Overall, we identified 7 transcripts showing parental bias in gene expression which were not reported in 4 other recent RNA-Seq studies of imprinting.CONCLUSIONS: Our methods and data provide a robust and high-resolution map of imprinted gene expression in the human genome.

U2 - 10.1186/s12915-019-0674-0

DO - 10.1186/s12915-019-0674-0

M3 - Article

VL - 17

SP - 50

JO - Biology

JF - Biology

SN - 2079-7737

IS - 1

ER -