Linking chromosome abnormality and copy number variation

Abstract

Nine out of 10 people has a chromosome copy number variation (CNV) of >1,000 bp of DNA. In some cases they are inconsequential, in other cases the variations cause disease or disability, and in most cases the relevance has not been elucidated. Several studies describe CNVs as "normal" biological variants while other studies suggest that CNVs may be associated with developmental disability. A concerted effort is needed to classify genes according to their dosage sensitivity, or to their lack of sensitivity. Over time, this effort will lead to the establishment of principles that permit the prediction of the consequence of any one genomic copy number change.

Making chromosome abnormalities treatable conditions

“…However, this is not as big a challenge as it may appear on first consideration. As we proposed several years ago, [Cody and Hale, ] emerging data from three different lines of research continue to support our hypothesis that only 5–10% of genes are dosage sensitive. First, was the discovery that principle contributors to normal genetic variation (i.e., without overt adverse phenotypic effect) are gene copy number variants (CNVs).…”

Establishing a reference group for distal 18q-: clinical description and molecular basis

“…We anticipate that the majority of these genes are unlikely to have a dosage effect (Cody and Hale 2011). Twelve of these genes have no data regarding dosage effects and most of these have no information on their biological function.…”

The African Bullfrog (Pyxicephalus adspersus) genome unites the two ancestral ingredients for making vertebrate sex chromosomes

“…At the same time, reductions in gene dosage are largely deleterious [13][14][15][16][17] . Mechanisms of dosage compensation, such as X-inactivation in eutherian mammals 18-20 and X-linked hyperexpression in lizards 21,22 are thought to help solve this problem.…”

“…A particular departure from autosomal characteristics is the phenomenon of heteromorphic sex chromosomes which differ in size and gene content. As sex chromosomes evolve, the sex chromosome associated with the heterogametic sex (either Y or W) can experience gene loss, rearrangements, and gains of heterochromatin that change chromosome size and reduce gene dosage on the gametologous X or Z chromosome, respectively 6-12 .At the same time, reductions in gene dosage are largely deleterious [13][14][15][16][17] . Mechanisms of dosage compensation, such as X-inactivation in eutherian mammals 18-20 and X-linked hyperexpression in lizards 21,22 are thought to help solve this problem.…”