Mining Novel Candidate Imprinted Genes Using Genome-Wide Methylation Screening and Literature Review

Author(s):Show less -

Bonaldi, Adriano ^[1] ; Kashiwabara, Andre ^[2] ; de Araujo, Erica S. ^[3] ; Pereira, Lygia V. ^[1] ; Paschoal, Alexandre R. ^[2] ; Andozia, Mayra B. ^[1] ; Villela, Darine ^[1] ; Rivas, Maria P. ^[1] ; Suemoto, Claudia K. ^{[4, 5]} ; Pasqualucci, Carlos A. ^{[4, 6]} ; Grinberg, Lea T. ^{[4, 7]} ; Brentani, Helena ^[8] ; Maria-Engler, Silvya S. ^[9] ; Carraro, Dirce M. ^[3] ; Vianna-Morgante, Angela M. ^[1] ; Rosenberg, Carla ^[1] ; Vasques, Luciana R. ^[1] ; Krepischi, Ana ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Rua Matao 277, BR-05508090 Sao Paulo, SP - Brazil

^[2] Univ Tecnol Fed Parana, Dept Computat, Ave Alberto Carazzai 1640, BR-86300000 Cornelio Procopio, PR - Brazil

^[3] AC Camargo Canc Ctr, Int Ctr Res, Rua Tagua 440, BR-01508010 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Sch Med, Dept Pathol, Brazilian Aging Brain Study Grp LIM22, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Sch Med, Div Geriatr, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Sch Med, Dept Pathol, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[7] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, 1500 Owens St, San Francisco, CA 94143 - USA

^[8] Univ Sao Paulo, Sch Med, Dept Psychiat, LIM23, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[9] Univ Sao Paulo, Sch Pharmaceut Sci, Av Prof Lineu Prestes 580, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Review article
• Source: EPIGENOMES; v. 1, n. 2 SEP 2017.
• Web of Science Citations: 2

Abstract

Large-scale transcriptome and methylome data analyses obtained by high-throughput technologies have been enabling the identification of novel imprinted genes. We investigated genome-wide DNA methylation patterns in multiple human tissues, using a high-resolution microarray to uncover hemimethylated CpGs located in promoters overlapping CpG islands, aiming to identify novel candidate imprinted genes. Using our approach, we recovered similar to 30% of the known human imprinted genes, and a further 168 candidates were identified, 61 of which with at least three hemimethylated CpGs shared by more than two tissue types. Thirty-four of these candidate genes are members of the protocadherin cluster on 5q31.3; in mice, protocadherin genes have non-imprinted random monoallelic expression, which might also be the case in humans. Among the remaining 27 genes, ZNF331 was recently validated as an imprinted gene, and six of them have been reported as candidates, supporting our prediction. Five candidates (CCDC166, ARC, PLEC, TONSL, and VPS28) map to 8q24.3, and might constitute a novel imprinted cluster. Additionally, we performed a comprehensive compilation of known human and mice imprinted genes from literature and databases, and a comparison among high-throughput imprinting studies in humans. The screening for hemimethylated CpGs shared by multiple human tissues, together with the extensive review, appears to be a useful approach to reveal candidate imprinted genes. (AU)

• FAPESP's process: 13/07480-8 - Genetic and epigenetic factors in the etiology of the cutaneous melanoma
• Grantee: Ana Cristina Victorino Krepischi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/00898-1 - Submicroscopic genomic imbalances associated with specific congenital abnormalities and mental deficiency phenotypes
• Grantee: Carla Rosenberg
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC