Consequences of Genomic Alteration Flashcards
What are the four varieties of genetic disorders?
Single gene disorders
Chromosomal disorders
Multifactorial genetic disorders
Somatic gene disorders
What is the definition of a mutation?
A permanent inheritable change in DNA
What is polymorphism?
The occurrence of multiple genotypes and natural variations in genomic DNA sequence in the general population
What are the five types of mutation?
Silent: single base change that does not result in an amino acid change
Missense: single base change that does result in an amino acid change
Nonsense: single base change that changes an amino acid into a stop codon
Frameshift: insertion/deletion of bases in anything other than a multiple of three
Splice donor: alteration of sequences for accurate splicing of introns
Indel: insertion/deletion of more than one base
What are some factors that determine whether a mutation is pathogenic?
Is splicing affected?
Is it a functionally important site?
Does the change relate to disease within a family?
What are loss of function mutations?
Produce a reduced amount of the gene product
No gene product comes from a null allele
Usually have no effect unless it has a dominant negative effect (mutated allele interferes with the normal one)
What is a gain of function mutation?
Produce an increased amount or activity of a product
What are the features of autosomal dominant inheritance?
Affects/transmitted by either sex
If one parent affected, 50:50 chance of offspring being affected
(Achondroplasia/ Marfan’s syndrome)
What are the features of autosomal recessive?
Affects/transmitted by either sex
If both parents heterozygous(unaffected), 25% chance of child being homozygous affected
(Phenylketonuria/Haemochromatosis)
What is lyonisation?
Females heterozygous for a sex-linked recessive mutant gene express the same phenotype as a male who is hemizygous for the mutation. This occurs when somatic cells key to the expression of a phenotype has random inactivation on the X-chromosome (which carries the normal alleles)
What is the pattern of X-linked recessive?
Affects mainly males (depending on lyonisation) but no male to male transmission
All daughters of an affected male are carries
50% chance of a child being given the allele
What is the pattern of X-linked dominant?
Affects either sex, but females more than males
Child on an affected female has 50% chance of being affected
For an affected male, all daughter but none of his sons will be affected
What is the pattern of Y-linked inheritance?
Only affects males
All sons of an affected male are affected
What are some complications to Mendelian pedigree patterns?
Nonpenetrance
Variable expression (eg anticipation)
New mutations
Common recessive conditions can look dominant even if they aren’t
