MAP7D2 is a brain expressing X-linked maternal imprinted gene in humans

Yo Niida,Akihiro Yachie

doi:10.1038/npre.2011.6684.1

Abstract

AbstractIncreasing evidence suggests imprinted genes influence mouse and human behaviors and cognitive functions. Unlike autosomal imprinted genes, X-linked imprinted genes are expressed in a sex-dependent manner because of male hemizygosity. Therefore, these genes could directly affect sex-specific brain functions and sex-biased vulnerability to psychiatric disorders such as autism1. Comparing lymphoblastoid cell lines (LCL) and peripheral blood mononuclear cells (PBMC) from healthy adult male and females, we identified MAP7 domain containing 2 (MAP7D2) as the first human X-linked imprinted gene. Both in LCL and PBMC, MAP7D2 expression was significantly suppressed in males by maternal imprinting. In each female LCL clone, MAP7D2 was expressed higher in paternally derived allele and was affected by X-chromosome inactivation. In female PBMC, however, reactivation of maternal MAP7D2 alleles was observed. MAP7D2 was expressed specifically in the brain among human tissues with unique isoforms. These results predict a crucial role of MAP7D2 for human sex-dependent neurobiological traits.

Highlights

Comparing lymphoblastoid cell lines (LCL) and peripheral blood mononuclear cells (PBMC) from healthy adult male and females, we identified MAP7 domain containing 2 (MAP7D2) as the first human X-linked imprinted gene
Both in LCL and PBMC, MAP7D2 expression was significantly suppressed in males by maternal imprinting
Because the early stages of established female LCLs are mixtures of Xp or Xm active clones but skew to one clone during a long culture, it is difficult to detect an X-linked imprinting gene affected by X chromosome inactivation

Summary

Introduction

Comparing lymphoblastoid cell lines (LCL) and peripheral blood mononuclear cells (PBMC) from healthy adult male and females, we identified MAP7 domain containing 2 (MAP7D2) as the first human X-linked imprinted gene. Both in LCL and PBMC, MAP7D2 expression was significantly suppressed in males by maternal imprinting. In each female LCL clone, MAP7D2 was expressed higher in paternally derived allele and was affected by X-chromosome inactivation.

Results

Conclusion