Two siblings with osteogenesis imperfect, but their parents are normal. Mechanism of inheritance is aEUR'
Germ line mosaicism In some autosomal dominant disorders examplifled by osteogenesis imperfecta, phenotypically normal parents have more than one affected child. - This clearly violates the law of inheritance. Studies indicate that gonadal mosaicism may be responsible for such unusual inheritance. Mosaicism It means than an individual has 2 or more different cell lines derived from a single Zygote. - The persons body' is made up of a combination of cells with and without mutation for a paicular disease. - Because the mutation remains limited to a small poion of all of the body's cells, these individuals show no sign of the disease. Germline mosaicism Germline mosacism results from a mutation that occurs postzygotically during early embryonic development. In these a poion of the egg or sperm cells of a parent carries the mutation. - Because the mutation affects only cells destined to form the gonads the gametes carry the mutation but somatic cells of the individual are completely normal. - A phenotypically normal parent who has germ line mosaicism can transmit the disease causing mutation to the offspring through the mutant gamete. - Because the progenitor cells of the gamete carry the mutation there is a definite possibility that more than one child of such a parent would be affected. - Obviously, the likelihood of such an occurrence depends on the propoion of germ cells carrying the mutation. Anticipation The signs and symptoms of some genetic conditions tend to become severe and appear at an earlier age as the disorder is passed from one generation to the next. - This phenomenon is called anticipation. Anticipation is most often seen with ceain genetic disorders of the nervous system such as Huntington's disease, Fragile x-syndrome and myotonic dystrophy. Anticipation typically occurs with disorders that are caused by an unusual type of mutation called a "trinucleotide repeat expansion". - A trinucleotide repeat is a sequence of three DNA building blocks (nucleotide) that is repeated a number of times in a row. - DNA segments with an abnormal number of these repeats are unstable and prone to errors during cell division. - The number of repeats can change as the gene is passed. from parent to child. - If the number of repeats increases it is known as trinucleotide repeat expansion. - In some cases the trinucleotide repeat may expand until the gene stops functioning normally,. - This expansion causes the feature of some disorders to become severe with each successive generation. Genomic imprinting People inherit two copies of their genes - one from their. father and one from their mother. Usually both copies of each gene are active or "turned on" in cells. But with genomic imprinting however, only one of the two copies is normally turned on. Which copy is active depends upon the parent of origin. Some genes are normally active only when they are inherited. from a person's. father, others are active only when inherited from a person's mother. These genes are called "imprinted genes" because the gene was epigenetically silenced or marked in either the egg or sperm. Silencing or imprinting usually happens through the addition of methyl groups during egg or sperm formation. An individual normally has one active copy of an imprinting gene. Improper imprinting can result in individual having two active copies or two inactive copies. - This can lead to severe developmental anomalies, cancer and other problems e.g., - Prader willi - Angelman syndrome - They are both linked to same imprinting region of chromosomes 15.
Anticipation
Genomic imprinting
Germ line mosaicism
New mutation