Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on July 14, 2010). Includes bibliographical references.

Congenital hypotrichosis in cattle is commonly referred to as "rat-tail" syndrome and is characterized by a dilution of black coat color and morphological changes to the hair shaft and tail switch. Two loci are involved in the inheritance of the rat-tail phenotype, the "extension locus" (MC1R) and an unknown locus. In order to express the rat-tail phenotype the animal must inherit at least one black allele at MC1R and be heterozygous at the unknown locus. The rat-tail locus was previously mapped to an 8.7 cM region of Bos Taurus autosome (BTA) 5. Pmel17 is known to be involved in the expression of pigmentation and maps to the same region of BTA5 as the rat-tail locus. Cattle from a population segregating for the rat-tail syndrome were sequenced at Pmel17 in order to identify putative causative mutations. Two mutations were detected, a three base pair (bp) deletion in exon 1 at codon 18 removing a leucine residue, and a single nucleotide polymorphism (SNP) at codon 612 resulting in an amino acid substitution (A?E). The 3-bp deletion in exon 1 of Pmel17 is in 100% concordance with the rat-tail phenotype in this research population and may be causative of the rat-tail phenotype.

Trichorhinophalangeal syndrome is a malformation syndrome characterized by craniofacial and skeletal abnormalities and is inherited in an autosomal dominant manner. We distinguish free subtypes on clinical and molecular level - TRPS I, TRPS II, TRPS III. All TRPS patients have sparse hair, a pear-shaped nose, a long flat philtrum, a thin upper lip and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations and short stature are present. The subgroups TRPS I and TRPS III are result of the mutated TRPS1 gene, which is maped into the 8q24 region. This gene is situated proximal of the EXT1 gene, both genes are affected in a subgroup of patients with TRPS II. These patients suffer more from multiple (cartilaginous) exostoses and mental retardation. In this work we performed molecular genetic analysis of a sample of 16 patients, 8 probands showed a TRPS phenotype and 8 probands had only isolated exostoses. The peripheral venous blood of patients was used to gain purified DNA, which was subsequently used to investigate the chromosome 8q24 region using MLPA ("multiplex ligation-dependent probe amplification"). This analysis revealed a deletion in 1 TRPS patient and 1 patient with exostoses. Sequencing of the TRPS1 gene coding exons in remaining 7 TRPS...