Related Experiment Video

Updated: Jun 18, 2026

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

Altered transmission of HOX and apoptotic SNPs identify a potential common pathway for clubfoot

Audrey R Ester1, Katelyn S Weymouth, Amber Burt

  • 1Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX, USA.

American Journal of Medical Genetics. Part A
|November 26, 2009
PubMed

Insights

Genetic factors like HOXA gene variants and insulin-like growth factor binding protein 3 (IGFBP3) may contribute to clubfoot development. Gene interactions involving HOX and apoptotic genes offer a new biologic model for this common birth defect.

Area of Science:

  • Genetics
  • Developmental Biology
  • Orthopedics

Background:

  • Clubfoot is a common birth defect affecting limb development, with multifactorial causes that remain poorly understood.
  • The HOXA and HOXD gene clusters and insulin-like growth factor binding protein 3 (IGFBP3) are crucial for limb and muscle morphogenesis, making them potential candidates for clubfoot etiology.

Purpose of the Study:

  • To investigate the association of single nucleotide polymorphisms (SNPs) in the HOXA, HOXD gene clusters, and IGFBP3 with clubfoot.
  • To explore potential gene-gene interactions between these candidate genes and previously identified apoptotic gene variants in clubfoot development.

Main Methods:

  • Genotyping of 20 SNPs from HOXA/HOXD clusters and 12 SNPs in IGFBP3 in discovery (multiplex/simplex families) and validation (simplex trios) samples.
  • Transmission disequilibrium testing was used to analyze SNP associations.
  • Analysis of gene-gene interactions, including those with CASP3 SNPs.

Main Results:

  • A specific SNP in the HOXA basal promoter region (rs3801776) showed significant altered transmission in both discovery and validation samples (P = 0.004 and 0.028).
  • An SNP in IGFBP3 (rs13223993) also demonstrated altered transmission in the discovery sample (P = 0.003).
  • Significant gene-gene interactions were found between HOXA, HOXD, IGFBP3 variants, and SNPs in apoptotic genes, particularly CASP3.

Conclusions:

  • Perturbations in HOX genes, specifically HOXA, and IGFBP3 are associated with clubfoot.
  • Gene-gene interactions between HOX genes, IGFBP3, and apoptotic pathway genes (like CASP3) suggest a combined role in abnormal muscle and limb development leading to clubfoot.
  • This study proposes a biologic model implicating genetic factors in the developmental failure of limb rotation in clubfoot.

More Related Videos

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

Generation of Chimeric Axolotls with Mutant Haploid Limbs Through Embryonic Grafting07:17

Generation of Chimeric Axolotls with Mutant Haploid Limbs Through Embryonic Grafting

Published on: January 29, 2020

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Pleiotropy01:33

Pleiotropy

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,...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...