A Minimalist Approach to Gene Mapping: Locating the Gene for Acheiropodia, by Homozygosity Analysis

Abstract

Acheiropodia is an autosomal recessive disease that results in hemimelia (lack of formation of the distal extremities). We performed a complete genome screen of seven members of an extended pedigree that included three siblings with acheiropodia. Homozygosity mapping was used to identify regions most likely to harbor the gene for acheiropodia in this pedigree. In these two key regions (14p and 7q), further genotyping of one additional affected member of this pedigree plus seven additional unaffected siblings provided evidence, through linkage analysis, that the 7q36 region contains the acheiropodia gene. In this region, a maximum two-point LOD score of 3.81 (4.2 with multipoint analysis) was achieved, and a homozygous haplotype spanning a region of 11.7 cM was seen in all affected in this pedigree. Finally, genotypic analysis of two additional cases of acheiropodia with no known relation to the other samples revealed homozygous sharing of a portion of the same haplotype on 7q36, which reduces the chromosomal location of the acheiropodia gene to an 8.6-cM region. Localization of this gene, at the screening level, by use of data from only three affected subjects, provides an example of how certain genes may be mapped by use of a minimal number of affected cases.

Association Between Human Polymorphic DNA Markers and Hypoxia Adaptation in Sherpa Detected by a Preliminary Genome Scan

“…Genetic adaptation to hypoxia could result from few oligogenes (Maniatis et al 2004;Morton, 2005). In this perspective the use of founder populations has been recognized as a powerful approach for gene discovery (Te Meerman et al 1995;Durham & Feingold, 1997;Fullerton et al 2002), and the number of individual samples can be successfully minimized without compromising the ability to detect linkage between polymorphic DNA markers and candidate genes (Escamilla et al 2000;Fullerton et al 2002).…”

Single nucleotide polymorphisms in chicken lmbr1 gene were associated with chicken growth and carcass traits

“…It is the key candidate gene affecting limb development of vertebrate, located in the key candidate region of human and mouse preaxial polydactyly (PPD) [1][2][3][4][5][6][7] . The level of lmbr1 transcripts was dramatically misregulated at E12.0 in mouse Hx (Hemimelic extra-toes) mutant [2] .…”

“…The level of lmbr1 transcripts was dramatically misregulated at E12.0 in mouse Hx (Hemimelic extra-toes) mutant [2] . The special deletion of exon 4 and surrounding ≈ 5kb sequence of c7orf2/lmbr1 were detected in human Acheiropodia (ACHP) [3,4] .…”

The second case of Horn Kolb Syndrome in the same woman in Turkey, diagnosed prenatally at 16 weeks of pregnancy

“…3 For the present case we could not demonstrate the mutation during the antenatal period and then postnatal chromosome analysis was not accepted by the family because of the economic difficulties. To our knowledge this is the first case of Horn Kolb Syndrome diagnosed antenatally.…”

“…The second case of Horn Kolb Syndrome in the same woman in Turkey, diagnosed prenatally at 16 weeks of pregnancy 3 In this case report we present the second case of Horn Kolb Syndrome from Turkey.…”