Molecular Genetics

Molecular Genetics - Molecular Genetics Mutations=...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Molecular Genetics Mutations= permanent changes in DNA (classical); can occur in genes for receptors, structural, enzymatic and cell growth regulation proteins Mutation in germ cell= transmitted to progeny (inherited disease) Mutation in somatic cell= not transmitted (cancer and some congenital malformations) Types of mutations: 1. Point— substitution of a single nucleotide base by a different base (missense) -- substitution of a single nucleotide base by a stop codon (nonsense); towards end probably little/no effect -- substitution of a single nucleotide base by a different base resulting in the same amino acid (synonymous) 2. Frameshift —deletion or insertion of base pair(s) (not a multiple of 3) that alters the reading frame of the DNA strand 3. Trinucleotide repeat— amplification of 3 nucleotide; dynamic—can change size in gametogenesis; unstable; **non mendelian 4. Splicing- change in genome that affects the structure or abundance of mRNA (can be either a point or frameshift mutation); activate different transcription sites **1, 2 and 4= mendelian disorders Consequence of mutation depends on location Atypical or NON-Mendelian Forms of Inheritance 1. triple repeat expansions: reported in many disorders, all of which are associated with neurodegenerative disorders; may involve any part of the gene (introns, exons, untranslated regions); result in loss of protein function (mutation in 5’ UTR= fragile X mental retardation) or gain of function (mutation in coding region—abnormal protein= Huntington’s disease); mutation is dynamic ; threshold for converting permutation to full mutation differs with each disorder; amplification occurs in either oogenesis (ex. Fragile X syndrome) or spermatogenesis (ex. Huntington’s disease) depending upon disorder; permutation risk= between normal and mutant number of copies; ALL have CG nucleotides; loci on X and autosomal; # of triplets is variable; when you reach the threshold you get mutation; amplification of specific sets of 3 nucleotides within the gene disrupts its function; in all cases, gene functions are altered by an expansion of repeats, but the precise threshold at which permutations are converted to full mutations differs with each disorder; expansion in fragile X= occurs in oogenesis; expansion in Huntingtons= occurs during spermatogenesis; expansion may involve any part of the gene and can be grouped into 2 broad categories: untranslated regions (fragile X) or coding regions (Huntingtons); mutations affecting non coding regions= loss of function because protein synthesis is suppressed; mutations affecting translated parts= abnormal proteins (Huntingtons=gain of function); gain of function mutations result in polyglutamine diseases ex. Fragile X Syndrome= characterized by mental retardation and an abnormality in the X chromosome; results from mutation in FMR1 gene (5’ UTR region) which is located at Xq27.3 ; most common causes of familial mental retardation; discontinuity of staining or
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 02/08/2012 for the course PATHOLOGY 3245 taught by Professor X during the Spring '11 term at UWO.

Page1 / 5

Molecular Genetics - Molecular Genetics Mutations=...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online