Human molecular cytogenetics: Diagnosis, prognosis, and disease management

Abstract

The year 2001 witnessed the sequencing of 90% of the euchromatic region in the human genome but the ultimate goal to delineate the positions of all genes is yet to be achieved. Fluorescence In Situ Hybridization (FISH) is one of the methods for localizing genes on chromosomes. In the present study, diagnostic utility of single-, dual-, and multicolor FISH was evaluated for prenatal diagnosis, cancer genetics, and screening of various congenital anomalies (sex chromosomal and autosomal). Centromeric probes for chromosomes X and Y were used for screening minor aneuploid cell lines (XXY, XO, and XXX) in the cases of primary amenorrhea and suspected Klinefelter syndrome. The cases with ambiguous genitalia were analyzed using a probe specific for the sex-determining region (SRY). Suspected cases of Down syndrome were subjected to FISH using probe specific for chromosome 21. FISH was also used to study gene alterations in retinoblastoma and myeloid leukemias. Prenatal diagnosis was done to screen for aneuploidies of chromosomes 13, 18, 21, X, and Y using FISH on uncultured cells from amniotic fluid and chorionic villi sampling. The screening for common aneuploidies was extended to abortuses from spontaneous abortions. Using FISH, low-level mosaicism could be identified in some cases of primary amenorrhea and suspected Klinefelter syndrome. Submicroscopic gene rearrangements could be detected using FISH in cases of ambiguous genitalia and cancers. Further interphase FISH could provide results within 24 hours. To conclude, FISH adds to the diagnostic utility of routine cytogenetics and its use on interphase nuclei overcomes the difficulty of conventional cytogenetics, thereby reducing the time between sampling and diagnosis to 24 hr.

Human interphase chromosomes: a review of available molecular cytogenetic technologies

“…mapped oncogenes, genes/genomic loci within microdeletion or microduplication regions) [ 3 ]. Therefore, it is not surprising that there are only few approaches using these DNA probes that are performed to detect well-known chromosomal rearrangements in cancer cells [ 87 - 89 ] and, more rarely, deletions/duplications in clinical populations [ 1 , 3 , 8 , 50 , 90 - 92 ]. However, FISH using site-specific probes is almost the unique way to visualize DNA sequences smaller than 1 Mb in interphase nuclei.…”

Ethical, social, and cultural issues related to clinical genetic testing and counseling in low- and middle-income countries: a systematic review

“…Genetic counseling assists individuals in understanding test results and their consequences. As technology has evolved and become increasingly more cost-effective, genetic testing services have been introduced in low-and middle-income countries (LMICs), usually through research initiatives [13][14][15][16][17][18] or formal international partnerships. 19,21,22 In contrast, genetic counseling has not developed in a similar robust fashion, and remains largely a Western concept and profession.…”

N-myc amplification was rarely detected by fluorescence in situ hybridization in retinoblastoma

“…Numerous advantages of FISH over other conventional methods have been reported including its sensitivity, speed, technical simplicity, accuracy, resolution, efficiency, and reproducibility [12][13][14][15][16]. Particularly, it is possible with FISH to discern intercellular heterogeneity in gene amplification and to localize the source of the amplified N-myc signal [17,18].…”