What is the gneeral onset of chromosomal, single gene, and multifactorial disorders?
Chromosomal: in utero/at birth
Single gene: at/near birth
Multifactorial: increasing after puberty and into adulthood
What is the law of segregation?
Every individual possesses a pair of alleles (assuming diploidy) for any particular trait and that each parent passes a randomly selected copy (allele) of only one of these to its offspring
What is the law of independent assortment?
Separate genes for separate traits are passed indepently of one another from parents to offspring.
What is a polymorphism?
existence of multiple alleles for a particular gene (>1% freq. for each allele)
What is codominance?
The expression of each allele can be detected (neither allele is dominant)
What does it mean to be:
Metacentric: having the centromere in the middle
Sumetacentric: having the centromere somewhat distant from the middle
Acrocentric: having the centromere near the telomere
(short arms have distinctive structure, and contain mostly satellite sequences - short, simple sequence repetitive DNA - and multiple copies of the genes for ribosomal RNA)
How are short and long arms of chromosomes labeled?
Short = p
Long = q
Exact multiple of the number of chromosomes in a normal gamete
At least one set of chromosomes incomplete (usually a loss or gain of a single chromosome)
More than two complete sets of chromosomes
What causes aneuploidy?
Aneuploidy arises during mitosis or meiosis through nondisjunction:
- faliure of chromosomes to separate normally
What is Klinefelter Syndrome?
Associated with tall stature, postpubertal testicular failure and azoospermia (no sperm)
What is XYY Syndrome?
Tall staure and an increased incidence of speech delay
What is Turner Syndrome?
Short stature, amenorrhea, infertility and somatic abnormalities
What is XXX syndrome?
47, XY or XX, +21
Head and facial abnormalities
variable mental retardation
Extra copy of part of a chromosome leading to partial trisomy
Breakage and rejoining of a chromosome segment in reverse order
pericetnric: if centromere is included
paracentric: if centromere not included
deletion of telomeres and fusion of the broken ends to form ring
- very unstable during mitosis and frequently lost
Segment of one chromosome inserted intoa non-homologous chromosome
chromosome having one arm duplicated and the other arm lost; arises when the centromere divides abnormally and can involve eitehr the short (ISO p) or long (ISO q) arm
exchange of chromosome segments between non-homologous chromosomes
- Two main types are:
Reciprocal translocations: Material is simply exchanged between two Ch.
Robertsonian translocations: Fusion at centromere between two acrocentric chromosomes, with the loss of the short arms and the satellites
What are features that characterize autosomal recessive inheritance on a pedigree?
- Pedigree shows horizontal transmission; siblings are affected but not their parents or other relatives (1/4 siblings on average)
- Only homozygous or compound heterozygous individuals express trait
- Males and females equally affected
- If both parents affected; all children affected
- Pedigrees often show consanguineous matings
- In most cases, if 1 parent is affected and other is not, all children will be normal; unless normal parent is a carrier
What are features that characterize Autosomal dominant inheritance?
- Trait is transmitted vertically from one generation to another without skipping generations
- Both males and females are affected and transmit trait with equal probability
- each affected individual has one affected parent and unaffected family members do not transmit trait
What can lead to autosomal dominance?
- Dominant Negative Effect
- Gain of Function
What is Haploinsufficiency?
Dominance is due to the fact that half the normal amount of protein is insufficient to maintain normal function
What is Dominant Negative Effect?
The product of the mutant allele interferes with the product of another, normal, allele, resulting in overall adverse outcome
What is Gain-of-Function?
Dominant disorders can result from a change in the level of activity of a protein, or its expression in the wrong tissue or at the wrong time
What are features that characterize X-linked recessive disorders?
- Males are affected much more than females
- All the daughters of an affected father receive the mutant allele and are carriers, and will pass the trait onto half their sons - Daughters are obligate heterozygotes
- Father to son transmission is never seen
- Affected females have affected fathers and affected or carrier mothers
What are features that characterize X-linked dominant disorders?
- The trait does not skip generations
- Mothers transmit the trait to about half the children, both daughters and sons (assuming heterozyguos mom)
- Fathers transmit the trait to all daughters but no sons
- Within the population, females are affected about twice as often as males
What is locus heterogeneity?
Multiple mutant proteins in the same pathway cause the same disease
What is allelic heterogeneity?
Different mutations in the same gene cuse the same disease
What is penetrance?
The likelihood taht the disease allele will result in the disease
- If the mutation is not fully penetrant, an individual may carry the mutant gene, but may be asymptomatic
What does it mean to be a germline mosaic?
Only some of the cells in that person are mutant and depending on which cells/tissues have the mutation, the individual could be clinically normal, yet be able to pass it to their proginy
What is pleiotropy?
Diverse effects of a single gene on several organs
- frequently show variable expressivity (which differs from penetrance)
How does penetrance differ from variable expressivity?
Penetrance = All or nothing
Variable Expressivity = Different expressions of the disorder due to the gene's effects on the organs