Genetic diseases L29 Flashcards
What is penetrance?
Penetrance refers to the probability of a gene or trait being expressed. In some cases, despite the presence of a dominant allele, a phenotype may not be present. One example of this is polydactyly in humans (extra fingers and/or toes). A dominant allele produces polydactyly in humans but not all humans with the allele display the extra digits. “Complete” penetrance means the gene or genes for a trait are expressed in all the population who have the genes. “Incomplete” or ‘reduced’ penetrance means the genetic trait is expressed in only part of the population. The penetrance of expression may also change in different age groups of a population. Reduced penetrance probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown. This phenomenon can make it challenging for genetics professionals to interpret a person’s family medical history and predict the risk of passing a genetic condition to future generations.
What is expressivity?
Expressivity refers to variation in phenotypic expression when an allele is penetrant(i.e. expressed). Back to the polydactyly example, an extra digit may occur on one or more appendages. The digit can be full size or just a stub. Hence, this allele has reduced penetrance as well as variable expressivity. Variable expressivity refers to the range of signs and symptoms that can occur in different people with the same genetic condition. As with reduced penetrance, variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified. If a genetic condition has highly variable signs and symptoms, it may be challenging to diagnose.
How can we classify disorders?
-Single-gene (changes) with large effects ( this is passed on through Mendelian genetics) Examples of this include cystic fibrosis, Sickle cell anamia -Chromosomal disorders (these are rare but have high penetrance) e.g. down syndrome -Complex multigenic Disorders more than one gene associated with the condition each variant has low penetrance and small effect individually.
What are some examples of mutation types?
-Point mutations -Frameshift mutations -Contiguous mutations - nucleotides may be repeated multiple times -Copy number variation (CNV) an entire gene may be accidentally repeated.
What are the different types of Contiguous mutations?
Di-nucleotide repeats i.e. bases CA are repeated multiple times Tetra-nucleotide i.e. bases CAGA are repeated multiple times Tri-nucleotide repeats i.e. bases CAG are repeated multiple times.
What are the three types of point mutations?
Silent/synonymous - does not affect the amino acid sequence as the code is degenerate ( i.e. different codons code for the same amino acid) Missense/nonsynonymous - change in amino acid sequence Nonsense/nonsynonymous- change in an amino acid sequence which leads to a premature stopping i.e. the change in the codon meant it was read as a stop codon. synonymous meaning no change
What does it mean to have a conservative change to an amino acid sequence?
The amino acid sequence is changed yet still retains biochemical properties.
What does it mean to have a non-conservative change to an amino acid sequence?
The amino acid sequence is changed and does not still retain the same biochemical properties..
When does insertion or deletion not cause a frameshift?
When there is insertion or deletion of three bases
From which parent does mitochondrial inheritance occur?
Your mother
What is a multifactorial mutation/inheritance?
Many factors are involved in causing the defect
Why can X linked diseases not be passed on via the father?
Because X chromosmes are usually the ones that carry the allele forn the disease and are passed on by the mother whereas Y chromosomes are passed on by the father.
What are de novo mutations?
Mutations not inherited by parents
Does autosomal dominance have variable expressitivity despite high penetrance?
Yes
What is Marfan syndrome?
Autosomal dominant syndrome which affects the fibrillin 1 structural glycoprotein expressed in ciliary zonules which can cause subluxation of lens.
What are the three types of chromosomal aberations?
Translocations Isochromosomes Deletions/Ring/inversions.
