Characterization and mapping of four novel human expressed polymorphic trinucleotide microsatellites

Area of Science:

• Genetics
• Molecular Biology
• Bioinformatics

Background:

• Pathological expansion of trinucleotide microsatellites causes several human genetic diseases.
• Identifying new disease-associated loci requires characterizing more expressed trinucleotide repeat-containing regions.

Purpose of the Study:

• To search the expressed sequence tag database (dbEST) for novel trinucleotide repeat loci.
• To characterize these loci for their potential role in expansion diseases.

Main Methods:

• Searched dbEST for repetitive trinucleotides, selecting four loci for study.
• Utilized PCR amplification for size polymorphism identification and chromosomal mapping.
• Employed somatic hybrid and radiation hybrid panels for mapping.
• Performed database searches (GenBank, dbEST, UniGene) to identify EST clusters and construct contigs.

Main Results:

• Four novel trinucleotide repeat loci (EST00586, EST05486, EST13299, HHEA48B) were identified and characterized.
• Size polymorphism and chromosomal locations were determined for each locus.
• EST clusters were found for three loci, enabling contig construction and identification of a partial open reading frame in one instance.
• Three loci showed linkage to autosomal dominant diseases with unknown genetic defects.

Conclusions:

• The expressed sequence tag database (dbEST) is a valuable resource for identifying candidate loci for new trinucleotide repeat expansion diseases.
• Further characterization of these loci may aid in understanding the genetic basis of certain human diseases.