Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization

Abstract

This disclosure relates to a method of specifically decorating selected mammalian chromosomes and of detecting, identifying and and / or quantitating selected individual chromosomes, by means of chromosomal in situ suppression (CISS) hybridization. The method is useful in analyzing cells for the occurrence of chromosomes, chromosome fragments or chromosome aberrations.

Description

FUNDING [0001] Work described herein was supported by Grant Numbers GM-32156 and CA-15044 awarded by the National Institutes of Health. The United States Government has certain rights in the invention.BACKGROUND [0002] Chromosome banding techniques have facilitated the identification of specific human chromosomes and presently provide the major basis upon which chromosomal aberrations are diagnosed. The interpretation of chromosome banding patterns requires skilled personnel and is often technically difficult, especially with respect to detecting minor structural changes and when analyzing complex karyotypes, such as those of highly aneuploid tumor cells. An additional complexity is that readable metaphase chromosome spreads are sometimes very difficult or impossible to prepare from certain cell types or tissues. Alternative methods for identifying chromosomal aberrations would be valuable because they could augment current methods of cytogenic analysis, particularly if such alterna...

AI Technical Summary

Benefits of technology

[0005] The method of the present invention, referred to as CISS hybridization, is particularly useful because it can be used to specifically stain individual mammalian chromosomes at any point in the cell cycle. It can be used to assess chromosomal content, particularly chromosome aberrations (e.g., deletions, rearrangements, change in chromosome number) which, until the present invention, have been time-consuming and / or difficult, if not impossible, to detect. The method is useful in providing a rapid and highly specific assessment of individual mammalian chromosomes in any context (e.g., diagnosis and / or monitoring of a genetic condition or a disease state) in which such an assessment is desired.

Problems solved by technology

The interpretation of chromosome banding patterns requires skilled personnel and is often technically difficult, especially with respect to detecting minor structural changes and when analyzing complex karyotypes, such as those of highly aneuploid tumor cells.

An additional complexity is that readable metaphase chromosome spreads are sometimes very difficult or impossible to prepare from certain cell types or tissues.

All chromosome-specific repetitive DNAs reported to date are localized to discrete subregions of each chromosome and, thus, such DNA probes are unsuitable for analyses of many types of chromosomal aberrations (e.g., translocations and deletions).

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