Non-Mendelian Inheritance Patterns by B. Korf | OPENPediatrics скачать в хорошем качестве

Non-Mendelian Inheritance Patterns by B. Korf | OPENPediatrics

In this video, Dr. Korf talks about sex-limited inheritance, epistasis, digenic inheritance, anticipation in the role of triplet repeat expansion mutations, genomic imprinting, and mitochondrial inheritance. Please visit: www.openpediatrics.org OPENPediatrics™ is an interactive digital learning platform for healthcare clinicians sponsored by Boston Children's Hospital and in collaboration with the World Federation of Pediatric Intensive and Critical Care Societies. It is designed to promote the exchange of knowledge between healthcare providers around the world caring for critically ill children in all resource settings. The content includes internationally recognized experts teaching the full range of topics on the care of critically ill children. All content is peer-reviewed and open access-and thus at no expense to the user. For further information on how to enroll, please email: [email protected] Please note: OPENPediatrics does not support nor control any related videos in the sidebar, these are placed by Youtube. We apologize for any inconvenience this may cause. My name is Bruce Korf. I'm a Medical Geneticist at University of Alabama at Birmingham. This lecture will focus on non-Mendelian inheritance patterns. This lecture will explain the following ideas: sex-limited inheritance, epistasis, digenic inheritance, anticipation in the role of triplet repeat expansion mutations, genomic imprinting, and mitochondrial inheritance. In sex-limited expression, a phenotype is only seen either in males or females but not in both. The example here is that of male pattern baldness, which is typically expressed only in males. It is an autosomal dominant trait, but females have a low likelihood of manifestation. In this case then, a female has transmitted the trait and could be said to be non-penetrant having an affected father and an affected son. Other examples of sex-limited expression would be hereditary breast and ovarian cancer, where obviously ovarian cancer does not occur in men, and breast cancer only rarely does. Epistasis involves the influence of one gene on the expression of another. The classic example involves the ABO blood group system. This system is a two-allele system in which individuals with the A allele produce an antigen on red blood cells called A, and those with the B allele, an antigen called B. Heterozygotes, who have an A and a B allele will produce both antigens. If you look at the pedigree above, you see a male with type A blood and a partner with type O blood had a child with type AB. This would seem to be impossible, because the mother does not have a B allele to transmit in this pedigree. What actually is going on though is an example of an epistatic interaction. The enzymes that are the product of the A or the B allele act on a substrate, the H substance, which is a precursor either to A or B. H itself is the product of another enzymatic reaction from a previous precursor. Individuals who have what is called the Bombay phenotype fail to produce H because of a deficiency of the enzyme required to go from the precursor to the H substance. These individuals then fail to make either the A or the B antigen, but not because they lack the A or the B enzyme, but rather because they lack the H substance. So one can presume that the mother in this case has this phenotype due to mutation in an enzyme upstream of the A or the B enzymes. In this case, therefore, the enzyme that would act to produce H substance acts in an epistatic manner to produce a phenotype similar to deficiency of the A or B enzyme. Digenic inheritance is a relatively recently discovered phenomenon in which heterozygosity for two distinct genes can produce a phenotype that otherwise would require homozygosity for one or the other gene. Consider this pedigree where there are two gene loci, and this individual is heterozygous for a mutation in locus 1, and this individual heterozygous for a mutation in locus 2. Notice that this child inherits the locus 1 and locus 2 mutations and is affected, even though he is not homozygous for either one. There are a number of disorders where this digenic inheritance pattern has been identified, most notably retinitis pigmentosum. Neither allele, if heterozygous by itself, would be sufficient to produce the phenotype. This tends to occur when the gene products interact with one another and when a partial deficiency of one compounded with a partial deficiency of another leads to inadequate function and, hence, a phenotype.