Genetics Basis/Muts/Path Flashcards
3 Positions of Centromere
Metacentric
Submetacentric
Acrocentric
Pseudoautosomal Pairs (PARs)
X and Y share 2 regions of homology which undergo high levels of recombination
XIST
Gene only expressed on inactive X to cause inactivation
Lyon Hypothesis (3)
In female somatic cells, X inactivation occurs early, is random, and is clonal
Unbalanced or “Skewed” X Inactivation
When mutation of X linked disorder is on active X and normal allele on inactivated X, so a female carrier of X linked disorder can present with it
Prophase I
Time of recombination/crossing over
3 Types of Mutations
Numerical chromosome abnormalities
Structural Chromosome Abnormalities
Gene mutations
2 Kinds of Aneuploidy
Trisomy 21: 47 chroms, Down syndrome
Monosomy X: 45 chroms, Turner syndrome
Unbalanced Structural Abnormalities
Extra or missing chromosome portions can lead to a clinical phenotype
Balanced Structural Abnormalities
Misplaced chromosome portions not associated w/ clinical phenotype
Robertsonian Translocation
Occurs to combine acrocentric chromosomes, karyotype is 45 and progeny may have Down syndrome
Di/polygenic
Disease that is caused by the combined effect of mutations in two/multiple genes
Epigenetic Factors
Hereditary factors that are independent of actual DNA sequence
5 Mechs of Imprinting-Related Disorders
Microdeletion w/ loss of nonimprinted gene copy Uniparental disomy (UPD) - 2 homologous chroms from same parent Mut in the nonimprinted copy of gene Mut affecting the imprinting control region Imbalance bw maternally and paternally imprinted genes that have an antagonistic effect
Important Result from Imprinting
***Have to inherit 1/2 of chromosomes from mom and 1/2 from dad
Pharmacogenetics
Study of the impact of single genetic variants on drug metabolism/action
Pharmacogenomics
Study of drug metabolism in relation to the whole genome or individual’s overall genetic constitution
Pharacokinetics
Representation of body’s action on the drug
Pharmacodynamics
Effect the drug has on the body
Therapeutic Window
Drug dosage that can treat disease effectively while staying in safety range
2 Phases of Drug Metabolism/Elimination
I: Modification of chemical, usually rendering it more polar so it can be assessed by subsequent enzymes
II: attachment of polar, ionizable group to the respected molecule (usually so it can be secreted)
Cytochrome P450 (4)
Monooxygenase in microsomes (vesicles made from ER membranes) that often metabolize drugs and account for genetic variation causing individual variation to many medications
Warfarin (4)
Anticoagulant with wide range of dosage whose effect depends on a cytP450 and an enzyme involved in clotting factor pathway
Malignant Hyperthermia (4)
AD
Mutations in ryanodine R and calcium channel that lowers threshold for muscles to fire spontaneously, and anesthesia further lowers this level causing them to fire
Pseudocholinesterase Variants
Defective variants of enzyme that breaks down muscle relaxants like succinylcholine, causing apnea that lasts for hours
G6P Dehydrogenase Deficiency (3)
X linked so mainly affects males, reduced capacity to fight free radicals and get hemolytic crises
Acute Intermittent Porphyria (3)
Autosomal dominant deficiency in enzyme in pathway for heme production - cyt p450 activating drugs like barbituates trigger
4 Risk Factors for Dizygotic Twins
Ethnic background of mother
Maternal age
Reproductive medicine techniques
Undetermined genetic factors
Twin-Twin Transfusion Syndrome
In monochorionic pregnancies only, one fetus transfuses blood into other twin, resutling in anemia, intrauterine growth retardation, and death in donor
Conjoined Twins
Monozygotic twins whose failed separation results from twinning process initiating approximately 13 to 14 days after fertilization
Turner Syndrome
Female w/ 1 X so no Barr bodies
Fragile X Syndrome (3)
XLR so mainly in boys
Causes autism
From trinucleotide repeats
Myotonic Dystrophy
Trinucleotide disease that presents earlier/more severely w/ more repeats
Phenylketouria (4)
AR mutation of impaired phenylalanine hydroxylase activity, causing intellectual disability and seizures and others
Pleiotropy
Different mutations in same gene can be responsible for development of different disorders
Genetic Heterogeneity
Same disorder can be triggered by muts in different genes
Osteogenesis Imperfecta (3)
Dominant negative mutation
2 Types: Type I (mild) collagen degraded after formed
Type II: (severe) mutated procollagen
Prader Willi Syndrome (cause + 4 symptoms)
From lack of paternal gene, causes hypotonia, feeding problems, truncal obesity, hypogonadism
Angelman Syndrome (cause + 4 symptoms)
From lack of maternal gene, causes severe ID, epilepsy, inappropriate laughter, ataxia
Pallister-Killian Syndrome
Potentially lethal disorder w/ major visceral anomalies, pigmented skin, facial dysmorphism
Incontinentia Pigmenti
XLD that affects ectodermal derivatives like skin/hair/teeth/nails/eyes/brain
Neurofibromatosis (3)
Autosomal dominant disease w/ variable expressivity, can have just small lumps on skin or large internal/external plaque things
Ectrodactyly (3)
Autosomal dominant split hand deformity w/ reduced penetrance
Familial Testotoxicosis/Precocious Puberty
Male-limited autosomal dominant disorder
Retinitis Pigmentosa
Dramatic locus heterogeneity that can cause progressive/peripheral visual loss and poor dark vision
Pyloric Stenosis
Multifactorial disease w/ sex bias, 5:1 more common in males
Cystic Fibrosis
AR disorder w/ respiratory and bowel problems, as well as male infertility
Waardenburg Syndrome
AD problem causing hearing loss among other things
Duchenne Muscular Dystrophy
XLR disease causing muscular development problems, resorting to Gower’s maneuver to stand
Van der Woude Syndrome (4)
Autosomal dominance w/ reduced penetrance and variable expressivity
Can cause lip pits in mild or cleft lip in severe
