Genetics Flashcards
Genetics
The study of heredity
Genetic disease
a disease caused by a mutation in the genetic material
Congenital disease
A disease present at birth
Epigenetics
the study of changes in gene function that occur without a change in the DNA of this gene
Examples of Codominance
MHCs and ABO blood group
Meiosis I
Replication and separation of chromosomes to make 2 cells that are diploid
Meiosis II
Separation of sister chromatids and cell division leading to haploid gametes
Homologous recombination
Sister chromasomes lined up on the metaphase plate have a crossing over of chromatids which resolves switching some genetic material from one to the other
Metacentric Chromosome
P and Q arm are same length
Submetacentric
P arm is shorter than Q arm
Acrocentric
P arm is almost completely nonexistent
Diploid human genome
46, XX or 46 XY
Chromosomes 1-22 Autosomes
Arranged in Karyotype Largest to smallest
Karyotype Nomenclature
Total number of Chromosomes
Sex Chromosomes
Any Chromosomal Abnormalities
Chromosomal Disorders
Aneuploidy: loss or gain of a chromosome
Polyploidy: the presence of one or more additional sets of chromosomes
How does aneuploidy occur
Non-disjunction
Mostly occurs during oogenesis in females
More likely at later age
Trisomy 21
Down Syndrome Growth retardation Mental retardation Early onset alzheimers 40% risk congenital heart disease 15-20 fold risk of Leukemia
Trisomy 13
Patau Syndrome Severe facial dismorphism Cardiac malformations 50% die within first week of life Rest die by 6 months
Trisomy 18
Edwards Syndrome
Characteristic finger folding
Heart abnormalities
Survival beyond 1 year very unusual
45, X
Turner Syndrome Intrauterine Edema Neck Webbing Short Stature (SHOX) Infertility
47, XXY
Klinefelter Syndrome Tall Stature Gynaecomastia Infertility Mild learning deficits
47, XXX
Triple X
No physical abnormalities
Normal fertility
Mild learning difficulties
47, XYY
XYY Tall Stature Normal fertility Mild learning difficulties Some behavioral issues
Balanced vs. Unbalanced Chromosome Rearrangement
Balanced: No loss or gain of essential chromosome material
Unbalanced: Loss or gain of essential chromosome material
Translocations
Reciprocal: balanced unless breaking point is through a gene
Robertsonian: Accentric chromosomes, balanced because P arm has little gene info
Inversions
Pericentric: include the centromere
Paracentric: Dont include centromere
Isochromosomes
Centromere splits so P arms join together and Q arms join together
Williams Syndrome
Caused by microdeletions Distinct facial appearance Cardiovascular abnormalities Mental retardation Distinct cognitive profile
What are the consequences of chromosomal structural abnormalities
Very little effect on individual
Can lead to mitotic spindles abnormalities leading to increase in partial trisomy or monosomy
Haploinsufficiency
Mutation in a gene leads to absence of half a signal that requires the full stimulation to work
(Familial Hypercholesteremia)
Dominant Negative Effect
Mutant Protein interferes with function of a normal protein Osteogenesis imperfecta Types 1 (1/2 normal amount) Type II (mutation in protein leads to 1/4 normal amount
Gain of function
New property of a protein
Achondroplasia: Mutation of FGFR3 results in overactive receptor
Huntington Disease: Mutant protein is cytotoxic
Allelic Heterogeneity
Different alleles can effect the same function. Presence of different nonfunctional alleles can cause problems that look like a double mutation
RET Gene
Locus Heterogeneity
Mutations on different genes can have the same effect
New Mutations
Spontaneous mutation rate (Extremely rare)
Incomplete Penetrance
Some conditions do not manifest even in people who are dominant for the mutation
Delayed onset
Diseases that manifest later in life may be passed on to offspring.
Someone can die before manifesting the disease
Gonadal Mosaicism
People can have some gametes with a mutation and some that don’t carry it
Pleiotropy
Single gene with diverse effects
All the conditions caused by Marfan Syndrome related to fibrillin gene mutation and weak connective tissue
Variable Expressivity
Some people express more or less severe symptoms of the same disease
Why are there differences in penetrance and expressivity
Modifier Genes
Environmental Factors
Complex genetic interactions
What can happen to histones
Acetylation: More gene expression HAT acetylates N termini, HDAC removes it
Methylation: Less expression, Lysine residues of carboxyl termini
Phosphorylation
Rett Syndrome
Neurological disorder in girls
Mutations of MECP2 protein lead to altered expression of brain function genes
X inactivation
Equalizes the contribution of X chromosome in males and females
Random X is inactivated
Mechanism of X inactivation
XIST RNA codes for DNA methylation, alteration of chromosome structure, and barr body formation
XIC is Xq13.2
Anticipation
Increased severity of disease in successive generations caused the continued expansion of repeats
Mechanism of expansion thought to be slipped mispairing
CAG repeats
Huntington’s disease
Gain of function mutation leads to toxic protein
CTG repeats
Myotonic Dystrophy
Repeats cause DNA to hairpin resulting in changes to RNA splicing
GAA repeats
Friedrich Ataxia
CGG repeats on FMR1 genes
Fragile X syndrome Mental retardation Distinct facial morphology X linked recessive Break at Xq27.3
Genomic Imprinting
Prader Willi (Paternal imprinting on chromosome 15, hypotonia, hypogonadism, obesity) Angelman Syndrome (Maternal imprinting, Seizures, severe mental retardation, unprovoked smiling, lack of speech)
