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Related Concept Videos

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Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...
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The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo
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Placental multi-omics integration identifies candidate functional genes for birthweight.

Fasil Tekola-Ayele1, Xuehuo Zeng2, Suvo Chatterjee2

  • 1Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. ayeleft@mail.nih.gov.

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|May 2, 2022
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Summary

This study links genetic variants to birthweight by analyzing placental gene expression and DNA methylation. Findings reveal how placental function influences birthweight and future cardiometabolic health.

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Area of Science:

  • Genetics
  • Epigenetics
  • Developmental Biology

Background:

  • Abnormal birthweight increases later-life cardiometabolic disease risk.
  • Placental function is crucial for fetal development but underrepresented in genomics.
  • Mechanisms linking genetic variants to birthweight remain unclear.

Purpose of the Study:

  • To investigate the functional mechanisms connecting genetic variants to birthweight.
  • To integrate placental epigenetic and gene expression data with genome-wide association study (GWAS) loci.
  • To elucidate the role of placental pathways in regulating birthweight.

Main Methods:

  • Analysis of placental DNA methylation and gene expression data.
  • Integration with established GWAS loci for birthweight.
  • Multi-trait colocalization analysis to identify effector genes.

Main Results:

  • Identified placental methylation and gene expression targets for birthweight GWAS loci.
  • Target genes are enriched in cardiometabolic, immune, and hormonal pathways.
  • Demonstrated causal influence of methylation on WNT3A, CTDNEP1, and RANBP2 expression; identified PLEKHA1, FES, CTDNEP1, and PRMT7 as likely effector genes.

Conclusions:

  • Placental epigenetic and transcriptomic mechanisms are key to genetic regulation of birthweight.
  • These findings provide mechanistic insight into birthweight regulation and its link to cardiometabolic health.
  • The study highlights the placenta's role in mediating genetic influences on birthweight and long-term health outcomes.