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Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 pairs of autosomes and one pair of sex chromosomes. A human female has two X chromosomes, while a male has one X chromosome and one Y chromosome.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Learning about the X from our parents.

Alison S Wise1, Min Shi2, Clarice R Weinberg2

  • 1Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park Durham, NC, USA ; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.

Frontiers in Genetics
|February 26, 2015
PubMed
Summary
This summary is machine-generated.

Researchers developed a new method, the parent-informed likelihood ratio test for the X chromosome (PIX-LRT), to improve genetic association studies. This method enhances power for detecting genetic effects on the X chromosome, particularly for complex diseases.

Keywords:
SNPsX chromosomeassociation studycase-parent triadfamily-based designlikelihood ratio testoral cleft

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Area of Science:

  • Genetics
  • Statistical Genetics
  • Human Genetics

Background:

  • The X chromosome is understudied in genetic association studies due to limited methodological options.
  • Existing methods often extend the transmission disequilibrium test (TDT) for nuclear-family-based studies.

Purpose of the Study:

  • To introduce a novel statistical method, the parent-informed likelihood ratio test for the X chromosome (PIX-LRT), for association studies.
  • To enhance statistical power by utilizing parental genotype information and offspring sex.

Main Methods:

  • Developed the PIX-LRT method for analyzing case-parent triads.
  • Incorporated parental genotype information and offspring sex for increased statistical power.
  • Utilized the Expectation-Maximization algorithm to handle missing parental genotypes.
  • Calculated non-centrality parameters to assess power gain and robustness compared to alternative methods.

Main Results:

  • The PIX-LRT method enables relative risk estimation under various inheritance models.
  • Applied PIX-LRT to public data from families with oral cleft.
  • Identified a strong, internally-replicated signal for a SNP marker associated with cleft lip with or without cleft palate.

Conclusions:

  • PIX-LRT offers a powerful new approach for X chromosome association studies.
  • The method effectively utilizes family structure and offspring sex to detect genetic associations.
  • Demonstrated the utility of PIX-LRT in identifying a genetic marker for oral cleft.