The Genetics of Birth Timing: Insights into a Fundamental Component of Human Development

Authors

  • BP Chaudhari,

    1. Departments of Pediatrics
    2. Developmental Biology
    3. Obstetrics and Gynecology
    4. Center for Preterm Birth Research
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  • J Plunkett,

    1. Departments of Pediatrics
    2. Developmental Biology
    3. Obstetrics and Gynecology
    4. Center for Preterm Birth Research
    5. Human and Statistical Genetics Program, Washington University School of Medicine, St. Louis, Missouri 63110, USA, and
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  • CK Ratajczak,

    1. Departments of Pediatrics
    2. Developmental Biology
    3. Obstetrics and Gynecology
    4. Center for Preterm Birth Research
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  • TT Shen,

    1. Departments of Pediatrics
    2. Developmental Biology
    3. Obstetrics and Gynecology
    4. Center for Preterm Birth Research
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  • EA DeFranco,

    1. Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, OH 45267
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  • LJ Muglia

    Corresponding author
    1. Departments of Pediatrics
    2. Developmental Biology
    3. Obstetrics and Gynecology
    4. Center for Preterm Birth Research
    5. Human and Statistical Genetics Program, Washington University School of Medicine, St. Louis, Missouri 63110, USA, and
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Louis J Muglia, MD, PhD
Department of Pediatrics,
Washington University School of Medicine,
660 S. Euclid Ave.
Box 8208,
St. Louis, MO 63110
Tel.: 314-286-2847;
fax: 314-286-2893;
e-mail: Muglia_L@kids.wustl.edu

Abstract

The timing of birth necessitates the coupling of fetal maturation with the onset of parturition, and occurs at characteristic, but divergent gestations between mammals. Preterm birth in humans is an important but poorly understood outcome of pregnancy that uncouples fetal maturation and birth timing. The etiology of preterm birth is complex, involving environmental and genetic factors whose underlying molecular and cellular pathogenic mechanisms remain poorly understood. Animal models, although limited by differences with human physiology, have been crucial in exploring the role of various genetic pathways in mammalian birth timing. Studies in humans of both familial aggregation and racial disparities in preterm birth have contributed to the understanding that preterm birth is heritable. A significant portion of this heritability is due to polygenic causes with few true Mendelian disorders contributing to preterm birth. Thus far, studies of the human genetics of preterm birth using a candidate gene approach have met with limited success. Emerging research efforts using unbiased methods may yield promising results if concerns about study design can be adequately addressed. The findings from this frontier of research may have direct implications for the allocation of public health and clinical resources as well as spur the development of more effective therapeutics.

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