Independent origin of 185delAG BRCA1 mutation in an Indian family.

BRCA1 and BRCA2 are the two major breast cancer susceptibility genes. We tested members of a family with multiple cases of breast cancer, for mutations in the BRCA1 gene. Analysis of the PCR amplicons of all the exons (22) of the BRCA1 gene using conformation sensitive gel electrophoresis (CSGE) revealed a heteroduplex band pattern in exon 2 of the proband (III-3) in this family. The amplicon was further sequenced to assess the nature of the mutation, which revealed a deletion of AG nucleotides at the 185th position (185delAG). The two base pair deletion introduces a stop codon at the 39th amino acid residue. A similar analysis was carried out on other extended family members to evaluate their allelic status. We detected the same deletion in 7 of the 19 members tested. Two of them are males. Haplotype analysis suggested an independent origin for this mutation. Our study highlights the importance of testing hereditary cases of breast/ovarian cancer for BRCA1 mutations in extended families in order to identify high-risk individuals at a pre-clinical stage and provide genetic counseling.

An analysis on gene architecture in human and mouse genomes.

A comparative genome analysis on exon-intron distribution profiles is performed for human and mouse genomes to deduce similarities and differences between them. Interestingly, both in human and mouse genomes, the total length in introns and intergenic DNA on each chromosome is significantly correlated to the chromosome size. The results presented provide a framework for understanding the nature and patterns of exon-intron length distributions, the constraints on them and their role in genome design and evolution.

Intron position conservation across eukaryotic lineages in tubulin genes.

A compilation of intron positions obtained from a large number of eukaryotic genomes across orthologous tubulins is explored for molecular evolution. Comparison of intron positions for 41 alpha, 80 beta, and 30 gamma tubulin genomic sequences indicates that the putative ancestral tubulin gene contained at least 19, 33, and 52 intron positions distributed at different sites in the coding regions for alpha, beta, and gamma tubulins, respectively. Many intron positions are old and are conserved across different eukaryotic lineages and intron distribution patterns are consistent with 'introns-early' hypothesis.

Human genome -- from pieces to patterns.

A profile of exon-intron lengths in genes shows a normal distribution. This observation suggests that different genes may have portions of their total exon and/or intron lengths in common. In order to explore the common exon-intron structural patterns that may arise due to common lengths across genes, we compared the exon-intron length patterns of annotated human genes. We discovered 1762278 conserved arrangements of exon-intron length across the otherwise unrelated and diverse genomic landscape. The existence of common exon-intron length patterns across unrelated genes suggests for their role of in gene assemblage and human genome design and architecture.

Alternatively spliced human genes by exon skipping--a database (ASHESdb).

UNLABELLED: Alternative splicing of mRNA allows many gene products with different functions to be produced from a single coding sequence. Exon skipping is the most commonly known alternative splicing mechanism. A comprehensive database of alternative splicing by exon skipping is made available for the human genome data. 1,229 human genes are identified to exhibit alternative splicing by exon skipping. AVAILABILITY: http://sege.ntu.edu.sg/wester/ashes/.

Introns and protein revolution--an analysis of the exon/intron organisation of actin genes.

A catalogue of intron positions obtained from a large number of actin genes has been compiled with a view to understanding the possible origin of intervening sequences. Actins are ubiquitous proteins conserved in evolution and an analysis of their gene structures from various organisms has revealed that there may be at least 25 intron positions distributed at different positions in the coding regions. A comparison of intron positions from a wide range of organisms from that of yeast to human actins shows that introns could be more ancestral in origin. The conservation in the observed intron patterns within the different tissue types hints at a possible functional significance of introns in present day actin genes.