Dataset Information

High-resolution linkage-disequilibrium mapping of the cartilage-hair hypoplasia gene.

ABSTRACT: We recently assigned the gene for an autosomal recessive skeletal dysplasia, cartilage-hair hypoplasia (CHH), to 9p21-p13 in Finnish and Amish families. An association was observed between CHH and alleles at D9S163 in both family series, suggesting that these loci are in linkage disequilibrium and close to each other. Here we extended these studies by exploiting the linkage-disequilibrium information that can be obtained from families with a single affected child, and we studied 66 Finnish CHH families with seven microsatellite markers. The analysis based on the Luria and Delbrück (1943) method and adapted to the study of human founder populations suggests that the distance between CHH and D9S163 is approximately 0.3 cM. An eight-point linkage analysis modified to take advantage of all possible information in 15 Finnish and 17 Amish families was capable of narrowing the likely location of CHH to within an interval of 1.7 cM on a male map. The peak lod score of 54.92 was attained 0.03 and 0.1 cM proximal to D9S163 on the male and female maps, respectively. These results confirm the power of genetic resolution, that lies in the study of linkage disequilibrium in well-defined founder populations with one major ancestral disease mutation.

SUBMITTER: Sulisalo T

PROVIDER: S-EPMC1918334 | biostudies-other | 1994 Nov

REPOSITORIES: biostudies-other

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High-resolution linkage-disequilibrium mapping of the cartilage-hair hypoplasia gene.

Sulisalo T T Klockars J J Mäkitie O O Francomano C A CA de la Chapelle A A Kaitila I I Sistonen P P

American journal of human genetics 19941101 5

We recently assigned the gene for an autosomal recessive skeletal dysplasia, cartilage-hair hypoplasia (CHH), to 9p21-p13 in Finnish and Amish families. An association was observed between CHH and alleles at D9S163 in both family series, suggesting that these loci are in linkage disequilibrium and close to each other. Here we extended these studies by exploiting the linkage-disequilibrium information that can be obtained from families with a single affected child, and we studied 66 Finnish CHH f ...[more]

PMID: 7977356

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Project description:Structural properties of articular cartilage such as proteoglycan content, collagen content and collagen alignment are known to vary over length scales as small as a few microns (Bullough and Goodfellow, 1968; Bi et al., 2006). Characterizing the resulting variation in mechanical properties is critical for understanding how the inhomogeneous architecture of this tissue gives rise to its function. Previous studies have measured the depth-dependent shear modulus of articular cartilage using methods such as particle image velocimetry (PIV) that rely on cells and cell nuclei as fiducial markers to track tissue deformation (Buckley et al., 2008; Wong et al., 2008a). However, such techniques are limited by the density of trackable markers, which may be too low to take full advantage of optical microscopy. This limitation leads to noise in the acquired data, which is often exacerbated when the data is manipulated. In this study, we report on two techniques for increasing the accuracy of tissue deformation measurements. In the first technique, deformations were tracked in a grid that was photobleached on each tissue sample (Bruehlmann et al., 2004). In the second, a numerical technique was implemented that allowed for accurate differentiation of optical displacement measurements by minimizing the propagated experimental error while ensuring that truncation error associated with local averaging of the data remained small. To test their efficacy, we employed these techniques to compare the depth-dependent shear moduli of neonatal bovine and adult human articular cartilage. Using a photobleached grid and numerical optimization to gather and analyze data led to results consistent with those reported previously (Buckley et al., 2008; Wong et al., 2008a), but with increased spatial resolution and characteristic coefficients of variation that were reduced up to a factor of 3. This increased resolution allowed us to determine that the shear modulus of neonatal bovine and adult human tissue both exhibit a global minimum at a depth z of around 100 microm and plateau at large depths. The consistency of the depth dependence of |G*|(Z) for adult human and neonatal bovine tissue suggests a functional advantage resulting from this behavior.

Dataset Information

High-resolution linkage-disequilibrium mapping of the cartilage-hair hypoplasia gene.

Publications

High-resolution linkage-disequilibrium mapping of the cartilage-hair hypoplasia gene.

Similar Datasets

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