Elevated DNA sequence diversity in the genomic region of the phosphatase PPP2R3L gene in the human pseudoautosomal region

Abstract

The evolution, inheritance and recombination rate of genes located in the pseudoautosomal region 1 (PAR1) is exceptional within the human genome. Pseudoautosomal genes are identical on X and Y chromosomes and are not inherited in a sex linked manner. Due to an obligatory recombination event in male meiosis, pseudoautosomal genes are exchanged frequently between X and Y chromosomes. During the isolation, characterization and sequencing of a novel gene PPP2R3L, which was classified by sequence homology as a novel member of the protein phosphatase regulatory subunit families, it became apparent that cosmids of different origin harboring this gene are highly polymorphic between individuals, both at the nucleotide level and in the number and sequence of tandem repeats.

Identity by descent and DNA sequence variation of human SINE and LINE elements

“…By using human samples from different continents, we also eliminated the ascertainment bias typical for analysis of polymorphisms within a single human population. The overall level of nucleotide diversity was slightly lower than that recorded for the genomic region of the phosphate PPP2R3L gene in the human pseudoautosomal region (Schiebel et al, 2000) and higher than that estimated for four-fold degenerate coding sites, two-fold degenerate sites and in 5) and 3) untranslated regions (Chakravarti, 1999). Also, these values were higher than those reported for a variety of nuclear non-Y chromosome DNA segments (Harding et al, 1997;Zietkiewicz et al, 1997;Clark et al, 1998;Cargill et al, 1999;Hacia et al, 1999;Harris and Hey, 1999;Jaruzelska et al, 1999;Fullerton et al, 2000;Wu et al, 2001).…”

Matrix-assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry-based Detection of Microsatellite Instabilities in Coding DNA Sequences: A Novel Approach to Identify DNA-Mismatch Repair-deficient Cancer Cells

“…Because of its high molecular resolution, excellent accuracy, reproducibility, and automation properties, this method offers the potential to replace other methods in molecular medicine (23)(24)(25)(26)(27)(28)(29). Although the feasibility of our semiquantitative approach has been demonstrated on HNPCC neoplasms and colorectal cancer cell lines, it may easily be adapted to MSI classification of cancers in other organs.…”

“…Methods commonly used for the detection of MSIs, including chromatography, electrophoresis, and DNA sequencing, are time-consuming and expensive and suffer from low sensitivity in the detection of quantitative differences. In this situation, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based genotyping offers a promising technical alternative (23)(24)(25)(26)(27)(28)(29). Here we describe a novel method for enhanced genotyping of MSIs that affect mononucleotide repeats with prospects for high throughput by use of MALDI-TOF-MS for semiquantitative analysis.…”

A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation as a determinant of cellular glycine receptor trafficking

“…As the human genome project progresses, more and more attention is paid to the genetic heterogeneity of individuals and populations. 36 It is expected that single nucleotide polymorphisms (SNP) emerge with a frequency of at least 1 : 1000. MALDI-TOF-MS analysis of SNPs or point mutations offers the potential for reliable high-throughput screening.…”