A View of Congenital Heart Defect Research by a Basic Scientist
In order to follow this discussion, you should know that genes are made up of a material known as DNA and they provide the plans or "blue prints" for individual proteins in the body. Genes are strung together on a large stretch of DNA which is known as a "chromosome". There is an average of about 4500 separate genes on each chromosome. Humans normally have 23 pairs of chromosomes and receive one of each pair from each parent. In order to turn a gene into a protein it is first copied from the chromosomes as mRNA and then them RNA is translated into a protein by a separate set of cellular machinery. When a gene is copied into mRNA and then protein, we say that it is "expressed". The proteins produced by a cell from mRNA are what make it functional. For example, a heart muscle cell contracts because it has expressed genes that code for specific proteins used for contraction. A liver cell expresses a different set of genes used for liver function such as detoxifying alcohol. Since all cells came from a single cell, it is the regulation of gene expression along the chromosome that makes cells different. There are about 100,000 genes in the human but each cell type expresses only 20,000-30,000 genes. Since the majority of these genes are needed by all cells for ordinary cellular processes, it is expected that less than 200 of the genes expressed in the developing heart will prove critical to CHD. Identification of when and where these specific genes are expressed is important in understanding how the embryonic heart develops.
Since each person has two sets of chromosomes, there are normally two copies of every gene. When a gene is expressed in a specific cell type, both copies of the gene are expressed. If one copy contains an error, the other copy is usually adequate for normal development. If an error in one copy of a gene produces a defect, the error is known as a dominant mutation. In DiGeorge or Velo-cardio-facial syndromes there is the loss or deletion of a stretch of one chromosome 22 containing a number of genes. Though we do not yet know which genes are missing in this area, normal development appears to require two copies of at least one of the genes in this region. If both copies of a gene must have an error before a birth defect is seen, then the error is known as a recessive mutation. Most gene mutations fit into this category. All of us probably carry genes with an error but it is only when this gene is combined with an error-containing gene from the other parent, and the embryo can’t make the right protein,that we see a genetic birth defect. There can also be problems with too many copies. Extra pieces of (or whole) chromosomes can get misplaced during formation of sperm or eggs and the embryo can end up with more than two copies of some genes. An extra chromosome is called a trisomy and an extra piece of a chromosome is called a partial trisomy. Down’s syndrome is caused by an extra copy of chromosome 21 (either a complete or partial copy). There is at least one gene on this chromosome that causes developmental defects when too many copies are present.
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