What is the Werner Syndrome?

Werner Syndrome and genetic     

    Predisposition for the Werner Syndrome inherited autosomal recessive. Autosomal means that both boys and girls can get the disease. Recessive means that changing the genetic predisposition is incidental to normal. Only when a child has inherit the sick gene of both father and mother, the disease manifested. People with only one change in the building have no symptoms and are called carriers. So you have 25% chance not to be gene carrier, 50% chance to gene carrier, and 25% chance of inheriting the disorder.

    The picture below shows how inheritance works!

    carriers

    For any offspring of a patient with Werner syndrome, the chances are very small because the risk of shifting the WRN gene carrier of a potential partner is very small. The overall probability of being a carrier is less than 1 in 500, the chance of offspring of Werner's syndrome is 1 / 2 times in 1 500, only 1 in 1000.

    The cause

    The cause was due to an inherited defect in the DNA. By a mutation (change) on chromosome 8 lacks the helicase enzyme. Throughout some of the DNA processn disrupted. There is an accelerated shortening of telomeres(ends of chromosomes), with the result that cells shorter life. Helicase, a group of enzymes that play an important role in DNA replication. Helicase provides despiralisatie DNA, DNA repair and the segregation of chromosomes. In Werner syndrome patients often seem much older than they are. Usually they are 20 years old estimated. The aging process in these patients is two times faster than normal.

    WRN was originally identified as a gene responsible for Werner Syndrome (WAS, 'Progeria of Adults "). The WRN gene consists of 35 exons that encode a protein of 1432 amino acids (Yu et al., 1998). WRN protein RecQ-type helicase domains in the central region (Gray et al., 1997) and exonuclease domains in the N-terminal region (Huang et al., 1998). Their preferred substrates appear different DNA metabolic intermediates, substrates which helicase and exonuclease activities are thought to function in a coordinated manner. The nuclear localization signal is present on the C-terminal region (Suzuki et al, 2001) .. Two consensus regions, RecQ helicase conserved region (RQC), the helicase RNaseD C-terminal conserved region (HRDC), present between the helicase and nuclear localization signal. The biochemical studies, combined with cell biological studies have suggested that this protein might be involved in DNA replication, repair, recombination, transcription, telomere maintenance and / or a combination of these events (eg, repair during replication). The majority of disease mutations result in truncations of the nuclear localization signals (Friedrich et al., 2010). Precise molecular mechanisms leading to mutations in WRN The WAS phenotype are being identified.

    wrn chromo

    WRN mutations in WAS patients.

    A diagram of the full-length wild-type WRN protein is shown with its N-terminus to the left (N) and the C-terminus on the right (C). Known functional domains are marked with dark shades, the exonuclease domain, the helicase domain, RecQ helicase conserved region (RQC), helicase RNaseD the C-terminal conserved region (HDRC), and nuclear localization signal (NLS). Mutations are grouped according to canonical classes and further identified by their amino acid changes. Splicing mutations are indicated by the affected exons. Splice a new splice site mutations (NSS) are as such. Genomic rearrangements or deletion (Del) or dual (DUP), are shown in the corresponding protein locations, regions beyond the figure in dotted lines. * Indicates uncertainty in the interpretation of array CGH results (Adapted from Friedrich et al., 2010).

    Human Aging Gene Found In Flies