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K D Tsuchiya

Publications and source records attributed to K D Tsuchiya.

5 recordsLinked to original sources
PubMed2002

Escape from X inactivation.

Although the process of X inactivation in mammalian cells silences the majority of genes on the inactivated X chromosome, some genes escape this chromosome-wide silencing. Genes that escape X inactivation present a unique opportunity to study the process of silencing and the mechanisms that protect some genes from being turned off. In this review, we will discuss evolutionary aspects of escape from X inactivation, in relation to the divergence of the sex chromosomes. Molecular characteristics, expression, and epigenetic modifications of genes that escape will be presented, including their developmental regulation and the implications of chromatin domains along the X chromosome in modeling the escape process.

Animals↗
PubMed2000

E-cadherin mutation-based genetic counseling and hereditary diffuse gastric carcinoma.

The E-cadherin mutation has been identified in a subset of families with multiple cases of diffuse gastric carcinoma. However, the true penetrance of this mutation and its association with other carcinomas in such families remains elusive. We aim to show the importance of DNA-based genetic counseling in hereditary diffuse gastric carcinoma. The proband was self-referred after three of his siblings died of diffuse gastric carcinoma. Medical and pathology records confirmed diagnoses. The family was educated about diffuse gastric carcinoma. Analysis for the 70G-->T mutation was performed by sequencing genomic DNA from lymphocyte pellets. DNA results and genetic counseling were provided individually to those tested. Twenty-four family members were tested for the E-cadherin mutation. Nine were found to be positive and 15 were negative. Three who tested positive and were affected are now deceased. None of the 19 patients counseled wanted results sent to their physicians once they recognized the potential for insurance discrimination. None had undergone endoscopic ultrasound. Three who were positive for the E-cadherin mutation expressed strong interest in prophylactic gastrectomy. The E-cadherin mutation strongly predicts susceptibility to diffuse gastric carcinoma. Emotional stress in at-risk patients, the limited knowledge of the mutation's penetrance, and limitations of available screening mandate patient-centered genetic counseling.

Cadherins↗
PubMed2000

Chromosomal domains and escape from X inactivation: comparative X inactivation analysis in mouse and human.

In females, most genes on the inactive X Chromosome (Chr) are transcriptionally silenced. However, several dozen genes have been identified in human that escape inactivation and are expressed from both the active and inactive X Chrs. Many of the genes that escape inactivation in human are subject to inactivation in mouse, raising questions concerning the mechanisms that govern expression from the inactive X Chr in the two species. In human, the existence of a cluster of genes in Xp11.21-p11.22 that escape inactivation suggests that control of X inactivation occurs at the level of chromosomal domains. In this study, we have isolated, physically mapped, and determined the X inactivation status of a number of the orthologous mouse genes that correspond to this human "escape domain". In contrast to human, only the mouse Smcx gene has been found to escape inactivation in this region thus far, despite a highly conserved physical map between the two species. Sequence analysis and functional characterization of the mouse Smcx promoter did not reveal any obvious unique features that would explain the difference in the behavior of this gene on the inactive X compared with other nearby genes. Possible mechanisms responsible for the differing inactivation status between genes in the escape domain in human Xp11. 21-p11.22 and the corresponding mouse region are discussed.

Animals↗
PubMed1998

Deletion 10q23.2-q23.33 in a patient with gastrointestinal juvenile polyposis and other features of a Cowden-like syndrome.

A cytogenetically visible interstitial deletion of chromosome band 10q23 was found in a 6-year-old boy with mental retardation, dysmorphic features, and juvenile polyposis coli. In order to map this patient's deletion physically, we performed fluorescence in situ hybridization by using yeast artificial chromosomes (YACs) in the vicinity of the deletion. Five YACs that span an 11-15 cM region within the deletion were identified. This patient's deletion contains the putative locus for Cowden syndrome and a recently discovered candidate tumor suppressor gene (MMAC1 or PTEN) that has been implicated in the progression of a variety of human malignancies. Furthermore, the deletion is near and possibly overlaps a locus associated with juvenile polyposis. The findings in this patient with a constitutional 10q23 deletion raise the issue of whether there are separate genes in this region that are involved in Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, juvenile polyposis, and tumor progression, or whether all of these entities could be due to a single gene.

Child↗