Mental retardation is hidden in the X chromosome
Men get mental retardation from women
Nadezhda Markina, Infox.ruMental retardation has a different nature.
Sometimes it is caused by gross chromosomal abnormalities, as in Down syndrome. But there are cases of hereditary mental retardation, which is transmitted with the X chromosome. This disease occurs almost exclusively in men, which is explained by the nature of inheritance. Women have two X chromosomes, and an unfavorable mutation on one copy is compensated by a normal gene on the other copy. But men have only one X chromosome - from the mother, so defective genes show their effect.
The disease was studied by scientists who made up a global scientific community – more than 70 researchers from the UK, Spain, Belgium, South Africa, the Netherlands, France, Germany, the USA, and Australia. The result of their five-year work is published in the journal Nature Genetics. "This is the largest DNA sequencing for the study of hereditary human diseases that has ever been carried out," says the head of the work, Professor Mike Stratton from the Wellcome Trust Sanger Institute in Cambridgeshire.
The male disease is transmitted with the female chromosome
Geneticists analyzed the X chromosome in 208 families where two or more cases of mental retardation were registered, which affects men, but is transmitted through the female line. Among them are families from the UK, other European countries, the USA, Australia and South Africa. In 203 families, DNA was taken from men, and in five – from female carriers who had a normal IQ. However, as the authors of the work clarified, from a genetic point of view, it does not matter whose DNA they used.
In 26.4% of cases, mental retardation in men was expressed in a strong degree (IQ 20-34), in 46.2% – in average (IQ 35-49) and in 24.5% – in moderate (IQ 50-69). The control group consisted of Europeans from healthy families.
There are theoretically several ways to find the genes associated with this disease on the X chromosome. Previously, scientists have already used methods to search for key sites by markers – DNA fragments, but a complete analysis of the entire X chromosome has not yet been carried out. For the first time in the world, such a large team of researchers was able to carry out sequencing – determining the sequence of nucleotides in the DNA chain of the entire X chromosome in groups of inherently dysfunctional and healthy families.
Scientists have sequenced 718 X-chromosome genes from 829 available in the database. Their task was to identify all variants of the nucleotide sequence (for example, replacing one nucleotide with another) and determine their relationship with the disease. Of the 1,769 variants found, 855 were observed multiple times, that is, they were found in the chromosomes of many hereditarily dysfunctional families. Obviously, they have a connection with the disease. Among them there were mutations that led to shortening of the amino acid chain of the synthesized protein, and those that made fragments of the DNA chain meaningless.
The wrong genes produce the wrong proteins As a result, geneticists have identified nine genes, mutations (variations of nucleotide sequences) in which are associated with X-chromosomal mental retardation.
These are the genes SYP, ZNF71, CASK, AP1S2, BRWD3, CUL4B, SLC9A6,UPF3 and ZDHHC9. They encode proteins that are somehow involved in cellular processes. Obviously, with a gene defect, these cellular processes are disrupted in the neurons of the brain.
Proteins of these genes are involved in the work of synapses – contacts between neurons (SYP, CASK), help vesicle vesicles carry a neurotransmitter molecule through the synaptic cleft (AP1S2), support the structure of chromatin – a complex of DNA with proteins (BRWD3), destroy meaningless RNAs (UPF3B). In addition, they are responsible for the modification of the amino acid sequence after its synthesis (ZDHHC9) and for ion exchange (SLC9A6).
With mutations in certain genes, mental retardation is complicated by other symptoms. There is epilepsy and impaired coordination of movements (SYP, SLC9A6), macrocephaly (BRWD3), relative macrocephaly, underdevelopment of the genitals, obesity and tremor (CUL4B), involuntary eye movements – nystagmus (CASK).
You need to know the enemy by sight Hereditary diseases transmitted with the X chromosome, which are affected in the vast majority of cases by men, have been studied by geneticists for 25 years.
Dr. Lucy Raymond from the University of Cambridge and Professor Mike Stratton from the Sanger Institute led a large-scale study to find new genes in which mutations lead to various hereditary diseases. Genetic analysis of mental retardation is an important stage in the cataloging of X-chromosome genes.
According to the authors of the work, the discovery of genes associated with this serious disease will allow families to have complete information about the risk of pathology in an unborn child in order to consciously plan their future.
Portal "Eternal youth" www.vechnayamolodost.ru23.04.2009