The gene is on the X chromosome, so women (circles) have two copies of it men (squares) have only one. The number of times that the trinucleotide CGG is repeated is given under the symbols. The above image shows the pattern of inheritance of the fragile X syndrome in one family. Females who inherit a fragile X (also from their mothers males with the syndrome seldom become fathers) are only mildly affected. Males who inherit such a chromosome (only from their mothers, of course) show a number of harmful phenotypic effects including mental retardation. This causes a constriction in the X chromosome, which makes it quite fragile. However, these longer repeats have a tendency to grow longer still from one generation to the next (to as many as 4000 repeats). The number of CGGs may be as few as 5 or as many as 50 without causing a harmful phenotype (these repeated nucleotides are in a noncoding region of the gene). A locus on the human X chromosome contains such a stretch of nucleotides in which the triplet CGG is repeated (CGGCGGCGGCGG, etc.). Several disorders in humans are caused by the inheritance of genes that have undergone insertions of a string of 3 or 4 nucleotides repeated over and over. Huntington's disease and the fragile X syndrome are examples of such trinucleotide repeat diseases. However, a number of inherited human disorders are caused by the insertion of many copies of the same triplet of nucleotides. Indels of three nucleotides or multiples of three may be less serious because they preserve the reading frame (see the above figure). Perhaps that is just as well as the protein would probably be too garbled anyway to be useful to the cell. Scroll up to see two other examples ( Patients C and D).įrameshifts often create new STOP codons and thus generate nonsense mutations. The mRNA is translated in new groups of three nucleotides and the protein specified by these new codons will be worthless. This figure shows how by shifting the reading frame one nucleotide to the right, the same sequence of nucleotides encodes a different sequence of amino acids. Indels involving one or two base pairs (or multiples of two) can have devastating consequences to the gene because translation of the gene is "frameshifted". Collectively, these mutations are called indels. The number can range from one to thousands. The protein produced by this patient had only the first 493 amino acids of the normal chain of 1480 and could not function.Įxtra base pairs may be added ( insertions) or removed ( deletions) from the DNA of a gene. In one patient with cystic fibrosis ( Patient B), the substitution of a T for a C at nucleotide 1609 converted a glutamine codon ( CAG) to a STOP codon ( TAG). People with cystic fibrosis inherit two mutant genes, but the mutations need not be the same. Unlike sickle-cell disease, then, no single mutation is responsible for all cases of cystic fibrosis. Defects in the protein cause the various symptoms of the disease. The numbers in the mutation column represent the number of the nucleotides affected. The gene encompasses over 188,000 base pairs on chromosome 7 embedded in which are 27 exons encoding the protein. The protein is responsible for transporting chloride and bicarbonate ions through the plasma membrane. Each of these mutations occurs in a huge gene that encodes a protein (of 1480 amino acids) called the cystic fibrosis transmembrane conductance regulator ( CFTR). Here is a sampling of mutations that have been found in patients with cystic fibrosis.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |