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Thursday, July 18, 2013

Genes and genetic disorders

If we think about how amazing it has been  the Human Genome project, how much we have learned from it and everything that has been generated so far, it's impossible to ignore the value of genomics, for example,  initially was thought that our 46 chromosomes were composed of 100,000 protein-coding genes, enzymes, hormones and overall regulatory sources of all life processes that shape human characteristics but now is possible to begin to manipulate all of them  to heal syndromes and diseases.

Chromosome 22 was the first to be fully identified 545 genes having assets, followed later by genetic mapping or sequencing of chromosome 21, with only 225 active genes, which opened the possibilities for genetic treatments medical situations as Down Syndrome, a form of Alzheimer's disease and various cancers.


Thus began the race to find a specific gene for each of the major conditions that afflict humans. At the same time, it have been found the relationship between the production of proteins and some genes that create on protein production and others that inhibit the production of the same.


In this sense it was found some genes associated with autism spectrum syndromes such as 15q11-q13, 2q37.3 or UBE3A for Angelman syndrome, which has also been associated with the GABRB3 gene, whereas for the syndrome Williams is the gene 7q11.23; MeCP2 for Rett syndrome, to mention only the best known developmental syndromes.


However, it is known that there are more syndromes, such as West syndrome that is associated with the ARX gene, or even lower prevalence may be mentioned De Lange syndrome or Crohn's disease, whose genetic alteration is in 5p13.1 gene.


Talking about less common syndromes we can talk about Smith-Magenis syndrome which is associated with  17p11.2 gene, or the VCFS 22q11 gene related, with myotonic dystrophy which is a multisystem disease whose genetic alteration is associated with the repetition CTG trinucleotide on chromosome 19.


While the tuberous sclerosis complex (TSC), which is an autosomal dominant inherited disease which may be due to the mutation of two distinct genes: TSC1 (9q34) and TSC2 (16p13.3).


Timothy syndrome caused by a mutation in the gene CACNA1C located in 12p13.3, other forms of alteration as 10p terminal deletion, has been associated with a phenotype similar to DiGeorg syndrome causing hiccups hyperparathyroidism, deafness sensory abnormalities stones.


Moreover, it has been  studied the gene involved with 45X/46XY mosaicism, or we can mention Cowden syndrome is associated with PTEN gene, which is located at 10q23.3.


Another group of genetic disorders like Goldenhar syndrome are related  to deletion 5q (Artigas-Pallares, Gabau-Vila & Guitart-Feliubadaló, 2005), all associated with developmental disorders.


Whereas if you look at the studies on cancer have been found, for example for brain cancer, NFkB protein with much higher activity than in normal brains or HER2 protein in lung and breast cancer, BCR- AB1 for chronic myelogenous leukemia, RAS, for several types of cancer, B-RAF for skin cancer, BCL-3 for lymphoma; RB1 for retinoblastoma, HNPCC for colon cancer and endometrial, the p53 gene causes cell suicide and is associated with cancer of the lung, colon, breast and brain (Collins and Barker, 2008).


It's not possible to forget disorders of cognitive processes such as Alzheimer's,  so it's possible to find genetic associations with cognitive processes, although further studies are not conclusive, for instance mentioned the IGF2R gene associated with intelligence, which is a very popular topic.


That is why around 1980 Dr. Plomin, from Institute of Psychiatry, at London, England, began his research on genes and intelligence relationship, since observed that two people with the same genes correlate as much as the same person performing an intelligence test with a year of difference, so he realized that identical twins who live apart are very similar or identical in intelligence tests that identical twins who live together, which is why it is considered that the environment influences the development of children, however it has become clear that genes can shape the brain in ways that make individuals better or worse to answer an intelligence test.


Despite this, Plomin suspect that more markers are needed to find the genes for intelligence, but states that exist many difficult to replicate details to affirm conclusively that have these genes (Silverman, 2008).



More consistently it was found the  called
language gene, which from the genetic standpoint is associated with the specific disorder of the cognitive process, which seems to be due to alteration of a small number of key genes and in particular FOXP2 gene mutation.


The gene in question is expressed primarily in certain areas of the central nervous system, both during embryonic development and in the adult individual, but is also expressed in other regions during embryo development, such as lung, intestine and heart, and in different tissues of the adult. However, affected individuals with language impairment, have a non-mutated copy of the gene (Burraco Benitez, 2005; 2006; Gopnik and Crago, 1991).



Although each day is more advanced in the study of genes and the proteome, considering that it is estimated that there are about 4000 genetic disorders, and so far has been identified only a little more than 60 genes involved in diseases, no doubt the work will take several years before conclusion, but in spite of all the implications of research some point that knowledge of the human genome will be the main focus in the diagnosis and treatment for a large number of diseases such as diabetes, cardiovascular disease, mental and many forms of cancer.


References: 

Artigas-Pallarés, J., E. Gabau-Vila, E., Guitart-Feliubadaló, M.  (2005) El autismo sindrómico: II. Síndromes de base genética asociados a autismo. Rev Neurol. 40 (Supl 1): S151-S162.

Benítez – Burraco, A. (2006) Genes y lenguaje. Teorema Vol. XXVI/1, 37-71.
           
Benitez-Burraco, A. (2005) FOXP2: del trastorno específico a la biología molecular del lenguaje. I. Aspectos etiológicos, neuroanatómicos, neurofisiológicos y moleculares. Rev Neurol.  40 (11): 671-682.

Collins, F. and Barker, A. (2008) Mapping the cancer genome. Scientific American Special Edition: New answers for cancer. Vol. 18. Num. 3. 22-29.

Gopnik, M. y M. B. Crago (1991) Familial aggregation of a developmental language disorder.  Cognition. 39. 1-19.

Hayden, KE., Strome, ED., Merret, SL., Lee, HR., Rudd MK., Willard, HF. (2013) Sequences Associated with centromere competence in human genome. Molecular and Cellular Biology. 33 (4) 763-772.

Weischenfeld, J., Symmons, O., Spitz, F.,&  Korbel, J. (2013) Phenotypic impact of genomic structural variation: insights from and for human disease. Nature Reviews Genetics. 14. 125-138.

 Young, E. (2013) Shutting down the extra chromosome in Down's Syndrom cells. National Geographic: Phenomena: Not exactly rocket science. Disponible en: http://phenomena.nationalgeographic.com/2013/07/17/how-to-shut-down-the-extra-chromosome-in-downs-syndrome/

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