Copy number will not reveal the epigenetic alterations in a damaged copy of gene from father.
Juani Mazmin Husin
41858996
Have you ever seen a baby with small birth weight, and later showed slow neurodevelopment and mild to moderate learning difficulties, starting to gain weight from the age of 2 and later on overeating, short adult stature, incomplete puberty and having difficulties in communicate appropriately? Do you know that the cause of obesity in child is not 100% due to consumption of fast food as claimed in the media? You might have heard about Prader Willi Syndrome(PSW), an extremely rare human genetic disorder which is believed to be the most common genetic cause of obesity. There is a loss of function of genes situated at 15q11-q13 and if the long q arm of one copy from the mother’s chromosome 15 is deleted, Angelman syndrome results. On the other hand, if the father’s copy of the chromosomal arm is deleted, Prader Willi Syndrome results. The mother’s genes in this are “turned off” through a rare phenomenon called genomic imprinting.The standard diagnosis of PSW includes both clinical observations and genetic investigations involving DNA methylation studies and fluorescence in situ hybridization (FISH) analysis. However, there are limitations on these analyses, which lead to a new designed using real-time PCR assay mainly to determine the size of the chromosomal deletions in patients with PWS. (Teresa Munce, et al). Genomic DNA isolated from both peripheral blood leukocytes and buccal epithelial cells were used in this study. Results were 100% concordant with previous FISH assays performed on the same patients, indicating that this assay is reliable and reproducible for detecting homozygous chromosomal detections.
Apart from the assay design, one must noted that a link between gene dosage and expression has not been experimentally determined in brain. A.Hogart et al have revealed that gene expression abnormalities were resulted from alterations in epigenetic regulations. Previous assumption that have been made was extra copy number of genes lead to increased in expressions. However, their study shows that gene expression can be altered in unexpected ways through epigenetic changes and it is likely that gene expression changes beyond the expected maternally expressed imprinted genes contribute to the variability in phenotypes in 15q11-13 duplication syndrome.
41858996
Have you ever seen a baby with small birth weight, and later showed slow neurodevelopment and mild to moderate learning difficulties, starting to gain weight from the age of 2 and later on overeating, short adult stature, incomplete puberty and having difficulties in communicate appropriately? Do you know that the cause of obesity in child is not 100% due to consumption of fast food as claimed in the media? You might have heard about Prader Willi Syndrome(PSW), an extremely rare human genetic disorder which is believed to be the most common genetic cause of obesity. There is a loss of function of genes situated at 15q11-q13 and if the long q arm of one copy from the mother’s chromosome 15 is deleted, Angelman syndrome results. On the other hand, if the father’s copy of the chromosomal arm is deleted, Prader Willi Syndrome results. The mother’s genes in this are “turned off” through a rare phenomenon called genomic imprinting.The standard diagnosis of PSW includes both clinical observations and genetic investigations involving DNA methylation studies and fluorescence in situ hybridization (FISH) analysis. However, there are limitations on these analyses, which lead to a new designed using real-time PCR assay mainly to determine the size of the chromosomal deletions in patients with PWS. (Teresa Munce, et al). Genomic DNA isolated from both peripheral blood leukocytes and buccal epithelial cells were used in this study. Results were 100% concordant with previous FISH assays performed on the same patients, indicating that this assay is reliable and reproducible for detecting homozygous chromosomal detections.
Apart from the assay design, one must noted that a link between gene dosage and expression has not been experimentally determined in brain. A.Hogart et al have revealed that gene expression abnormalities were resulted from alterations in epigenetic regulations. Previous assumption that have been made was extra copy number of genes lead to increased in expressions. However, their study shows that gene expression can be altered in unexpected ways through epigenetic changes and it is likely that gene expression changes beyond the expected maternally expressed imprinted genes contribute to the variability in phenotypes in 15q11-13 duplication syndrome.
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