Day1Part1-Pedigree,Mendel,Genome Organization Flashcards
Define: proband
AKA propositus or index case. The affected idiidual through whom a family with a genetic disortic is ascertained
Define: consultand
The individual (not necessarily affected) who presents for genetic evaluation and through whom a family with an inherited disorder comes to attention
Features of autosomal dominant inheritance
AKA “vertical inheritance.” Males and females equally affected. Can see male-to-male transmission. All affected individuals will have at least 1 parent who carries the allele. With each pregnancy; there is a 50% chance to offspring will inherit the disease.
Features of autosomal recessive inheritance
Males and females affected equally. Typically the parents are gene carriers. There is a 25% chance the offspring will be affected; a 50% chance the offspring will be a carrier; and a 25% chance will inherit no copies of the disease allele.
Features of X-linked dominant inheritance
When a female is affected; offspring has 50% chance for offspring to inherit the allele. When a male is affected all daughters will be affected but none of his sons. Only 1 copy of the allele is required. Males may be more severely affected
Features of X-linked recessive inheritance
Females are usually carriers and males are usually affected (they are hemizygous). For a carrier female; there is a 50% her sons will inherit the disease and a 50% chance her daughters will be carriers. An affected male will transmit the allele to all of his daughters and they will be carriers. No male to male transmission. If a woman is affected; all of her sons will be affected and all of her daughters will be carriers.
Penetrance
Fraction of individuals with a genotype who show manifestations of the disease. Analogous to a light swith (can be on or off). There is also age dependent penetrance
Expressivity
The degree to which a trait is expressed in an individual. Analogous to a light dimmer. Can be explained in part by sex; environment; stochastic effects; and modifier genes.
Sex limitation
Occurs if only one sex can express a phenotype (e.g. unicornuate uterus)
Sex influence
Phenotypic expression in some conditions is dependent on an individual’s sex (e.g. gout is more common in males)
Stochastic effects
Random effects
Modifier genes
Genetic factors outside of the genetic locus causing a disease can be important for the expression of Mendelian diseases
Phenocopies
Disease (traits) that are due to non-genetic factors
Pleiotropy
Used to describe multiple different phenotypic effects due to mutation(s) in a single gene. Ex. when there are symptoms in skin; nervous system; ocular; etc.
Euchromatic regions
More relaxed. Genome sequencing focused here but still not complete.
Heterochromatic regions
More condensed; more repeat-rich. Essentially unsequenced
How many SNPs are there in each person?
Average of 1 SNP every 1000 bp between any two randomly chosen human genomes
What are different regions of the genome?
Gene rich/gene poor; stable/unstable (disease associated); GC-rich/AT-rich (basis for chromosomal banding patterns)
What are the two classes of repetitive DNA?
Tandem repeats and dispersed repetitive elements
Describe 3 different kinds of tandem repeats
1-in different parts of genome; used for cytogenetic banding 2- a particular pentanucleotide sequence is part of human-specific heterochromatic regions on the
long arms of Chr 1; 9; 16 and Y (hotspots for humanspecific evolutionary changes) 3- alpha-satellite repeats
Describe alpha-satellite repeats
171 bp repeat unit near centromeres. May be important to chromosome segregation in mitosis and meiosis
Name 2 types of dispersed repetitive elements.
Alu family (eg of SINES-short interspesed repetitive elements); L1 family (eg of LINES).
Length and frequency of Alu family
~ 300 bps and 500;000 copies in genome
Length and frequency of L1 family
~ 6 kb and 100;000 copies in genome
