Maria Lagerström-Fermér

PubMed2002

Increased gene dosage at Xq26-q27 is associated with X-linked hypopituitarism.

We have identified a novel interstitial duplication at Xq26.1-q27.3 in a previously reported family with X-linked recessive hypopituitarism [1]. Mapping of the duplication was carried out using interphase FISH analysis of over 60 bacterial genomic clones from Xq25-q28. The proximal and distal breakpoints of the duplication are contained within the 432N13 and 91O18 clones, respectively, and are separated by approximately 9 Mb. Comparison with a recently published 13-Mb duplication in another XH family [2] indicated that the duplication break-points in these families were different. Therefore, we conclude that X-linked hypopituitarism is caused by increased dosage of a gene that is critical for pituitary development and that the causative gene is located within the 9-Mb duplicated region that we have defined.

Dosage Compensation, Genetic↗

PubMed2002

Comparative genomics by capture PCR.

There is increasing demand for efficient methods to relate genomic information from model organisms to other species of interest. Comparative genetic analyses are particularly valuable to identify functionally important sequence features on the basis of their evolutionary conservation. We demonstrate here how a single segment of just 32 or less conserved coding nucleotide positions can be used to isolate homologous gene sequences from large numbers of species using a single-sided PCR technique. The method was used to isolate and determine the 3'-untranslated sequence of the somatostatin gene from vertebrate species ranging from human to hagfish. Two sequence motifs centered an average 40-145 nucleotides downstream of the translational stop codon have remained conserved for up to 350 million years. One of the conserved tetrapod segments was used to select a primer for amplification of so-called comparative anchor tagged sequences (CATS) in regular PCR, and shown to amplify homologous sequences from DNA samples from 30 out of 33 tetrapods. In conclusion, we present a useful procedure to reveal functionally relevant sequence elements, and to select primers for amplification of homologous sequences from a wide range of species.

3' Untranslated Regions↗