MM 16-18 Flashcards
Which occurs more? Loss of protein function mutation or gain of protein function mutation?
Loss of protein
Mutation nomenclature: R408W
Arginine (R) at codon 408 becomes Tryptophan (W).
R408X would mean that Arginine was replaced with a stop codon.
del means deletion
Monogenic disease
Single gene defect
Locus heterogeneity
A disease that can have a phenotype upon mutations on several different genes. Normally the disease is the result of complex pathways or structures.
Allelic heterogeneity mutation and examples
A disease that arises from a mutation on one specific gene. The disease phenotype does not arise from mutations on other genes. Mutations can still come from different places on the gene and have different severities, but only the same gene is always involved in the disease.
PKU
Cystic Fibrosis
Compound heterozygosity
Compound heterozygosity is the condition of having two heterogeneous recessive alleles at a particular locus that can cause genetic disease in a heterozygous state.
For example, both alleles might be mutated but at different locations.
Complex inheritance
A disease that may not show Mandelian inheritance patterns to to its polygenic complexity and environmental factors. Eg, cardiovascular disease.
Polymorphic
Genetic predisposition for a disease due to mutations in many gene loci that each have a small contribution. Can be oligogenic or polygenic inheritance.
Epigenetics
Epigenetics studies genetic effects not encoded in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors that switch genes on and off and affect how cells express genes. They may or may not be heritable.
Eg. Methylation or Acetylation, tagging of DNA or histone to change the expression of a gene.
Genomic imprinting
Genomic imprinting is the epigenetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed. If the allele from the mother is imprinted, then only the allele from the father is expressed. There are about 60 known genes that undergo imprinting.
Disease can come when a mutation occurs on the active gene while the other is silenced.
X-chromosome inactivation
Women do not produce twice as many X encoded proteins as men. This is because one of the X-chromosomes (random) on women is inactivated early in embryonic life. Heterochromatin on the inactivated chromosome is condensed so that it cannot be transcribed, called a Barr-body.
Intermediate effect
Biochemically affected but clinically not.
X-linked recessive
Most X-linked diseases. A disease that is variably expressed in females and fully expressed in males.
Diseases are characterized as XLR or XLD based on how many females are clinically affected.
X-linked dominant
A disease that is expressed clinically in most people who carry the mutant gene. (Very Few disorders exist).
Inheritance patterns of X-linked recessive
Complete absence of male to male transmission. Mainly males effected in the pedigree.
If a mother is a carrier, she will pass the disease on the half of her sons and half of her daughters will be carriers.
If a father has the disease, half of daughters will be carries and sons will be neither carriers or have the disease.