Mutations in the Wolfram syndrome type 1 gene (WFS1) define a clinical entity of dominant low-frequency sensorineural hearing loss.

Objective: To describe low-frequency sensorineural hearing loss (LFSNHL) inherited as a dominant trait in 3 families and in 1 sporadic case.

Design: Longitudinal clinical study from 1968 to 2001.

Setting: Tertiary care hospital; field studies conducted by molecular genetic research laboratory.

Genetic maps of microsatellite and single-nucleotide polymorphism markers: are the distances accurate?

Genetic maps play an important role in gene mapping. Inaccurate genetic maps can hinder gene mapping by biasing lod scores and reducing the power to map a trait to a particular region. Although sequence-based physical maps can provide a unique order for markers, they do not provide information on genetic map distances.

Novel missense mutations and a 288-bp exonic insertion in PAX9 in families with autosomal dominant hypodontia.

We describe the molecular analysis of three families with hypodontia involving primarily molar teeth and report two novel mutational mechanisms. Linkage analysis of two large families revealed that the hypodontia was linked to the PAX9 locus. These two families revealed missense mutations consisting of a glutamic acid substitution for lysine and a proline substitution for leucine within the paired domain of PAX9.

A novel autosomal recessive non-syndromic deafness locus (DFNB35) maps to 14q24.1-14q24.3 in large consanguineous kindred from Pakistan.

Autosomal recessive nonsyndromic deafness is one of the most frequent forms of inherited hearing impairment. Over 30 autosomal recessive nonsyndromic hearing loss loci have been mapped, and 15 genes have been isolated. Of the over 30 reported autosomal recessive nonsyndromic hearing loss (NSHL) loci, the typical phenotype is prelingual non-progressive severe to profound hearing loss with the exception of DFNB8, which displays postlingual onset and DFNB13, which is progressive.

Map error reduction: using genetic and sequence-based physical maps to order closely linked markers.

The Marshfield comprehensive genetic maps are frequently used for linkage and association studies, however, for some regions of these maps the marker order has low level of likelihood ratio support. In order to investigate the level of statistical support and the accuracy of the genetic maps compared to sequence-based physical maps, two approximately 30 cM autosomal regions were selected. The first region was selected from chromosome 3 and consisted predominately of draft sequence.

Homozygosity mapping of a locus for a novel syndromic ichthyosis to chromosome 3q27-q28.

Ichthyosis is a heterogeneous group of skin disorders characterized by abnormal epidermal scaling. Occasionally, extracutaneous features are associated. A novel autosomal recessive ichthyosis syndrome is described here with scalp hypotrichosis, scarring alopecia, sclerosing cholangitis, and leukocyte vacuolization in two inbred kindreds of Moroccan origin.

Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse.

It has been demonstrated that the opioid peptide dynorphin plays a role in modulating responses to several psychoactive substances including cocaine. Our laboratory and others have found that mRNA levels of dynorphin in the caudate and putamen are elevated after acute or chronic cocaine exposure in rats. Recently, a 68-base pair (bp) repeat polymorphism within the core promoter region of the human prodynorphin gene has been reported to occur in alleles containing one, two, three, or four copies.

A susceptibility locus for migraine with aura, on chromosome 4q24.

Migraine is a complex neurovascular disorder with substantial evidence supporting a genetic contribution. Prior attempts to localize susceptibility loci for common forms of migraine have not produced conclusive evidence of linkage or association. To date, no genomewide screen for migraine has been published.

The map problem: a comparison of genetic and sequence-based physical maps.

The genetic order of autosomal genome-scan markers from Marshfield panels 9 and 10 were compared with their physical order, on the basis of the assembled nonredundant human genome sequence from the Human Genome Project-Santa Cruz (HGP-sc; October 2000 and April 2001 releases) and Celera (CEL; February 2001 release) databases. The genetic order of 96% of the markers on the Marshfield map for panel 10 is supported by a likelihood ratio of > or = 3 (odds ratio of 1,000:1). Inconsistencies with the genetic panel 10 map were found for 5% and 2% of the markers in the CEL and HGP-sc sequences, respectively.