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Biomedical subjects

Joanna Crawford

Publications and source records attributed to Joanna Crawford.

6 recordsLinked to original sources
PubMed2004

The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene.

The 16p13.3 breakpoints of two de novo translocations of chromosome 16, t(1;16) and t(14;16), were shown by initial mapping studies to have physically adjacent breakpoints. The translocations were ascertained in patients with abnormal phenotypes characterized by predominant epilepsy in one patient and mental retardation in the other. Distamycin/DAPI banding showed that the chromosome 1 breakpoint of the t(1;16) was in the pericentric heterochromatin therefore restricting potential gene disruption to the 16p13.3 breakpoint. The breakpoints of the two translocations were localized to a region of 3.5 and 115 kb respectively and were approximately 900 kb apart. The mapping was confirmed by fluorescence in situ hybridization (FISH) of clones that spanned the breakpoints to metaphase spreads derived from the patients. The mapping data showed both translocations disrupted the ataxin-2-binding protein 1 ( A2BP1) gene that encompasses a large genomic region of 1.7 Mb. A2BP1 encodes a protein that is known to interact with the spinocerebellar ataxia type 2 ( SCA2) protein. It is proposed that disruption of the A2BP1 gene is a cause of the abnormal phenotype of the two patients. Ninety-six patients with sporadic epilepsy and 96 female patients with mental retardation were screened by SSCP for potential mutations of A2BP1. No mutations were found, suggesting that disruption of the A2BP1 gene is not a common cause of sporadic epilepsy or mental retardation.

Adolescent↗
PubMed2002

CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3.

Numerous cytogenetic and molecular studies of breast cancer have identified frequent loss of heterozygosity (LOH) of the long arm of human chromosome 16. On the basis of these data, the likely locations of breast cancer tumor suppressor genes are bands 16q22.1 and 16q24.3. We have mapped the CBFA2T3 (MTG16) gene, previously cloned as a fusion partner of the AML1 protein from a rare (16;21) leukemia translocation, to the 16q24.3 breast cancer LOH region. The expression of CBFA2T3 was significantly reduced in a number of breast cancer cell lines and in primary breast tumors, including early ductal carcinomas in situ, when compared with nontransformed breast epithelial cell lines and normal breast tissue. Reintroduction of CBFA2T3 into different breast tumor derived cell lines with decreased expression of this gene reduced colony growth on plastic and in soft agar. CBFA2T3 was shown to function as a transcriptional repressor when tethered to the GAL4 DNA-binding domain in a reporter gene assay and, therefore, has the potential to be a transcriptional repressor in normal breast epithelial cells. Taken together, these findings suggest that CBFA2T3 is a likely candidate for the breast cancer tumor suppressor gene that is the target for the frequent 16q24 LOH in breast neoplasms.

Breast Neoplasms↗
PubMed2002

Is there a relationship between Wolfram syndrome carrier status and suicide?

Wolfram syndrome (WFS) is a rare, autosomal recessive neurodegenerative disorder. An increased risk of psychiatric disorders and suicide has been reported for heterozygote carriers. In this study we investigated whether mutations in the WFS gene are associated with suicide in the general population. The gene for WFS (WFS1) has recently been mapped to chromosome 4p16.1, and its genomic structure has been characterized. We screened the entire WFS1 ORF in a panel of 100 completed suicides, 60 blood donors not known to have psychiatric illness, and 100 donors with a negative history of depression or suicidal behavior. We did not find evidence of an increased incidence of WFS carriers in the suicide panel and concluded that WFS1 carrier status is not a significant contributor to suicide in the general population. Screening of this highly polymorphic gene resulted in the detection of 33 variants, 13 of which cause amino acid changes. Seven of these changes have not been previously reported and six were unique to our suicide panel.

Adult↗
PubMed2002

Sequencing, transcript identification, and quantitative gene expression profiling in the breast cancer loss of heterozygosity region 16q24.3 reveal three potential tumor-suppressor genes.

Loss of heterozygosity (LOH) of chromosome 16q24.3 is a common genetic alteration observed in invasive ductal and lobular breast carcinomas. We constructed a physical map and generated genomic DNA sequence data spanning 2.4 Mb in this region. Detailed in silico and in vitro analyses of the genomic sequence data enabled the identification of 104 genes. It was hypothesized that tumor-suppressor genes would exhibit marked mRNA expression variability in a panel of breast cancer cell lines as a result of downregulation due to mutation or hypermethylation. We examined the mRNA expression profiles of the genes identified at 16q24.3 in normal breast, a normal breast epithelial cell line, and several breast cancer cell lines exhibiting 16q24.3 LOH. Three of the genes, CYBA, Hs.7970, and CBFA2T3, exhibited variability ten times higher than the baseline. The possible role of these genes as tumor suppressors is discussed.

Breast Neoplasms↗
PubMed2002

Location and structure of the human FHR-5 gene.

The factor H family of genes has been localised to human chromosome 1q32. This region encodes various proteins involved in complement regulation and is known as the regulators of complement activation (RCA) gene cluster. The factor H genes encode seven known plasma proteins. Using fluorescence in situ hybridisation (FISH), radiation hybrid (RH) mapping and BLAST alignment analysis, we have established that the factor H-related 5 (FHR-5) gene is closely linked to the other factor H gene family members. Analysis of the genomic sequence indicates that the FHR-5 gene is situated between FHR-2 and the non-complement protein factor XIIIb (Fl3B). Like all members of the factor H family. transcription of FHR-5 is in the telomeric direction. Furthermore, the short consensus repeats (SCRs) of FHR-5 are encoded by individual exons and splicing is of type 1. These data allow the generation of a more complete map of the factor H gene family.

Base Sequence↗