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Scientific Reports Apr 2024All attempts to identify male-specific growth genes in humans have failed. This study aimed to clarify why men are taller than women. Microarray-based transcriptome...
All attempts to identify male-specific growth genes in humans have failed. This study aimed to clarify why men are taller than women. Microarray-based transcriptome analysis of the cartilage tissues of four adults and chondrocytes of 12 children showed that the median expression levels of SHOX, a growth gene in the pseudoautosomal region (PAR), were higher in male samples than in female samples. Male-dominant SHOX expression was confirmed by quantitative RT-PCR for 36 cartilage samples. Reduced representation bisulfite sequencing of four cartilage samples revealed sex-biased DNA methylation in the SHOX-flanking regions, and pyrosequencing of 22 cartilage samples confirmed male-dominant DNA methylation at the CpG sites in the SHOX upstream region and exon 6a. DNA methylation indexes of these regions were positively correlated with SHOX expression levels. These results, together with prior findings that PAR genes often exhibit male-dominant expression, imply that the relatively low SHOX expression in female cartilage tissues reflects the partial spread of X chromosome inactivation into PAR. Altogether, this study provides the first indication that sex differences in height are ascribed, at least in part, to the sex-dependent epigenetic regulation of SHOX. Our findings deserve further validation.
Topics: Child; Adult; Humans; Male; Female; Chondrocytes; Homeodomain Proteins; Short Stature Homeobox Protein; DNA Methylation; Epigenesis, Genetic; Cartilage
PubMed: 38580675
DOI: 10.1038/s41598-024-58530-9 -
Research Square Apr 2024Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. We assembled complete and gapless telomere to telomere (T2T)...
Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. We assembled complete and gapless telomere to telomere (T2T) Y chromosomes for these species. The pseudo-autosomal regions were similar in length, but the total chromosome size was substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity was accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 18MYA. The centromeres also differed dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosome have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.
PubMed: 38712074
DOI: 10.21203/rs.3.rs-4033388/v1 -
Human Molecular Genetics Feb 2024The UK Biobank is the most used dataset for genome-wide association studies (GWAS). GWAS of sex, essentially sex differences in minor allele frequencies (sdMAF), has...
The UK Biobank is the most used dataset for genome-wide association studies (GWAS). GWAS of sex, essentially sex differences in minor allele frequencies (sdMAF), has identified autosomal SNPs with significant sdMAF, including in the UK Biobank, but the X chromosome was excluded. Our recent report identified multiple regions on the X chromosome with significant sdMAF, using short-read sequencing of other datasets. We performed a whole genome sdMAF analysis, with ~410 k white British individuals from the UK Biobank, using array genotyped, imputed or exome sequencing data. We observed marked sdMAF on the X chromosome, particularly at the boundaries between the pseudo-autosomal regions (PAR) and the non-PAR (NPR), as well as throughout the NPR, consistent with our earlier report. A small fraction of autosomal SNPs also showed significant sdMAF. Using the centrally imputed data, which relied mostly on low-coverage whole genome sequence, resulted in 2.1% of NPR SNPs with significant sdMAF. The whole exome sequencing also displays sdMAF on the X chromosome, including some NPR SNPs with heterozygous genotype calls in males. Genotyping, sequencing and imputation of X chromosomal SNPs requires further attention to ensure the integrity for downstream association analysis.
Topics: Female; Humans; Male; UK Biobank; Biological Specimen Banks; Genome-Wide Association Study; Sex Characteristics; Chromosomes, Human, X; Genotype; Gene Frequency
PubMed: 38073250
DOI: 10.1093/hmg/ddad201