Biomedical subjects

Marijke J van Baren

Publications and source records attributed to Marijke J van Baren.

5 recordsLinked to original sources

PubMed2006

Iterative gene prediction and pseudogene removal improves genome annotation.

Correct gene prediction is impaired by the presence of processed pseudogenes: nonfunctional, intronless copies of real genes found elsewhere in the genome. Gene prediction programs frequently mistake processed pseudogenes for real genes or exons, leading to biologically irrelevant gene predictions. While methods exist to identify processed pseudogenes in genomes, no attempt has been made to integrate pseudogene removal with gene prediction, or even to provide a freestanding tool that identifies such erroneous gene predictions. We have created PPFINDER (for Processed Pseudogene finder), a program that integrates several methods of processed pseudogene finding in mammalian gene annotations. We used PPFINDER to remove pseudogenes from N-SCAN gene predictions, and show that gene prediction improves substantially when gene prediction and pseudogene masking are interleaved. In addition, we used PPFINDER with gene predictions as a parent database, eliminating the need for libraries of known genes. This allows us to run the gene prediction/PPFINDER procedure on newly sequenced genomes for which few genes are known.

Animals↗

PubMed2004

The PCR suite.

The web application PCR Suite is an extension of the primer design program Primer3. It allows the design of primer sets encompassing single nucleotide polymorphisms, all exons of a single gene, all open reading frames in a list of cDNAs or the creation of overlapping PCR products.

Algorithms↗

PubMed2002

Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.

The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease.

Alleles↗

PubMed2002

Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly.

Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (Ssq). The genetic lesions in both lie within the same respective intron of the LMBR1/Lmbr1 gene, which resides approximately 1 Mb away from Shh. Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh. This regulator is most likely the target for generating PPD mutations in human.

Animals↗

PubMed2002

A double RING-H2 domain in RNF32, a gene expressed during sperm formation.

The RING domain is a cysteine-rich zinc-binding motif, which is found in a wide variety of proteins, among which are several proto-oncogenes and the gene implicated in autosomal recessive juvenile parkinsonism, Parkin. The domain mediates binding to other proteins, either via their RING domains or other motifs. In several proteins, RING domains are found in combination with other cysteine-rich binding motifs and some proteins contain two RING domains. Recent evidence suggests that RING finger proteins function in the ubiquitin pathway as E3 ligases. A variant of the RING domain is the RING-H2 domain, in which one of the cysteines is replaced by a histidine. We have cloned and characterized a novel gene, RNF32, located on chromosome 7q36. RNF32 is contained in 37 kb of genomic DNA and consists of 9 constitutive and 8 alternatively spliced exons, most of which are alternative first exons. A long and a short transcript of the gene are expressed; the short transcript containing exons 1-4 only. This gene encodes two RING-H2 domains separated by an IQ domain of unknown function. This is the first reported gene with a double RING-H2 domain. In humans, RNF32 overlaps with a processed retroposon located on the opposite strand, C7orf13. RNF32 is specifically expressed in testis and ovary, whereas C7orf13 is testis-specific, suggesting that its expression may be regulated by elements in the RNF32 promoter region. RNF32 is expressed during spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation.

Alternative Splicing↗