Probability of Psychogenetic Disorders - Coursework Example

Download file to see previous pages They include the dosage effect, the direct damaging effect, or the position effect, where the gene in a new environment functions inappropriately (1). G-banding of chromosomes is one of the techniques used in cytogenetics. Other Cytogenetic techniques include Fluorescent in-situ hybridization, Centromere or C-banding, replication banding, Sub-microscopic telomere analysis, distamycin staining, and Comparative Genomic Hybridization (1). Abnormalities in chromosomes can also be identified by non-cytogenetic methods, that as Microarray analysis and Molecular analysis of Telomeric sequences (1). Human numerical abnormalities are now measured by the advent of cytogenetics, which includes Down`s Syndrome, Turner's syndrome, and Klinefelter`s syndrome. The advance of molecular cytogenetics started in the 1980s with the advent of Fluorescent in-situ hybridization. Later than FISH, the technique of chromosome microdissection came into the picture in which micromanipulation and examination of the chromosome were carried out. This method lead to the study in detail of the aberration in a chromosomal structure that could be isolated cloned and thereby studied in even finer detail. This method is also been put to medical use in the diagnosis of cancer and in hematological malignancies where it is used to determine the chromosomal translocations in the malignant cells, thus making the diagnosis easier and thereby the treatment becomes more specific. It is also used in the identification of the abnormality in myeloid leukemia (2). The future focuses on molecular cytogenetics including Comparative genomic hybridization microarrays; Single-Polynucleotide based Polymerization based karyotyping.  

A sample of Mrs. Krerr has been analyzed and karyotyping was carried out based on the G-banding Karyotype. There were clear indications of translocation between Chromosome 4 and 11 having t(4;11)(q21:p13) phenotype. Based on published literature and reports translocation in chromosome 4; 11 was found to be associated with high-risk infant acute leukemia (3) which arises due to illegitimate recombination between MLL and AF4 gene. Identification of this gene translocation in the early stage of the life cycle allows us to define the treatment regime in the subsequent development of diseases (4). The mechanistic aspect of this translocation is largely unknown but researchers can map the genomic breakpoints and, in this particular case it was found to be hyper-sensitive to Dnase I and the cleavage site for Topoisomerase II.

AF4p12, also known as the FRYL gene homologous to the Drosophila FRY gene could be involved in maintaining the integrity of polarized cells during morphogenesis (6).

Observed karyotype and interpretation need to be validated based on a little more cytogenetic analysis including Q- banding to obtain a high-resolution banding pattern to locate precise translocation. Similarly, NOR (Silver) staining will help to identify translocation due to the involvement of shorter arm translocation in a given sample. But it is highly recommended to use Q-PCR methodology using fusion-specific primer (i.e. primer which amplifies fusion region of MLL and AF4). The results of PCR amplification can be cross-verified using FISH where the amplicon of the fusion gene is used as a probe and hybridization will be performed on a normal individual’s chromosome spread. Results of Fusion amplification along with FISH analysis can be taken as concluding results to establish the disease's condition. Risk prediction based on mitotic segregation pattern should be evaluated with caution due to anomalies between theoretical segregation and actual segregation pattern. For example in the case of the carrier mother (heterozygotic for a rearrangement), the possibility of having an abnormal child remains at 10%, while 90% should be normal (9:1 ratio) but that is not the case in most of the events due to pattern of segregation of chromosome during meiosis which depends on how two chromosome align based on homologous search and then segregates. Thus, in most non-mendelian risk estimation, before estimating the risk one should take note of experience and reported incidence in literature.

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