Term
|
Definition
Pro: high titer, non-toxic
Con: small genome, non-integrating
Target: muscle, liver, brain |
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Term
|
Definition
big forehead and short limbs
autosomal dominant
lethal in utero to homozygotes
most common form of dwarfism
gain of function in FGFR3 gene
inhibits bone growth |
|
|
Term
|
Definition
Pro: high titer, cycling independent
Con: non-integrating, immune reaction
Target: cancer, immunization |
|
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Term
|
Definition
genetic imprinting
metnal retardation, seizures, "happy puppet syndrome",
maternal deletion with paternal imprinted on chromosome 15 |
|
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Term
| Becker Muscular Dystrophy |
|
Definition
| allelic with DMD, less severe, later onset, in-frame mutations, shortened-partially-functional protein |
|
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Term
| Beckwith-Wiedemann Syndrome |
|
Definition
example of a syndrome defect
heterogenous overgrowth (fat baby)
both IGF2 genes are expressed (maternal is normally imprinted)
normal intelligence, increased risk of tumors |
|
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Term
|
Definition
Symptoms: alopecia (loss of hair), ataxia, seizures, deafness, blindness, hypoglycemia, hyperammonemia, acidosis, late childhood or adolescence
Inheritance: autosomal recessive, esp. French Canadians
Biochemical: cannot release biotin from proteins for recycle, biotin is cofactor for 4 hydroxylase
Treatment: newborn screening, biotin daily |
|
|
Term
Breast cancer
Risk, risk related genes |
|
Definition
Risk in women 1/8
BRCA1: 50-80% breast, 40-60% multifocal brest, 15-45% ovarian
BRCA2: 50-85% breast, 10-20% ovarian, 6% male breast |
|
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Term
|
Definition
Metabolizes wafarin/coumadin
Related to VKORC1 gene inhibition |
|
|
Term
| Charcot-Marie-Tooth (CMT) disease, type 1 |
|
Definition
Symptoms: distal wasting and weakness, loss of reflexes, loss of sensation, onion-bulb
Inheritance: autosomal dominant, duplication of struture protein for PNS myelin (PMP-22)
Biochemical: segmental demyelination of neurons, altered nerve velocity, |
|
|
Term
|
Definition
Symptoms: neonatal onset, elevated sweat chloride, chronic cough, fatty stools, jaundice, clubbing, lung disease and liver failure
Inheritance: autosomal recessive (esp. Caucasian), allelic heterogeneity
CFTR gene (cAMP activated chloride channel), commonly delta-F508 deletion of Phe; plymorphisms of intron 8 (9Ts normal, 5Ts CF)
Biochemical: effects outwardly retifying chloride channels and a sodium channel; delta-F508 has abnormal protein folding -> impaired protein trafficking
Treatment: depends on type of defect |
|
|
Term
| Cytochrome P450 2D6 (CYP2D6) |
|
Definition
| Metabolizes codeine to morphine |
|
|
Term
|
Definition
| Low AFP, low uE3, high hCG, high inhibin, low PPAP-A in first trimester |
|
|
Term
| Duchenne Muscular Dystrophy |
|
Definition
Symptoms: 3-6years onset, muscle wasting, Gower sign (rise with press on thighs), walk on toes, pseudo-hypertrophy of calves, resp. or cardiac failure, elevated creatine kinase
Inheritance: x-linked recessive, 33% new mutations, 15% germline mosaic of mom, DMD gene
Biochemical: dystrophin protein part of muscle and neuron cytoskeleton and ECM |
|
|
Term
|
Definition
split hand deformity
locus heterogeneity
reduced penetrance (80%) |
|
|
Term
| Edwards syndrime Tri 18 positive tests |
|
Definition
| Low AFP, low uE3, low hCG, low PPAP-A |
|
|
Term
|
Definition
skin hyperextensibility
different mutations at different loci
auto dom, auto rec, X-linked |
|
|
Term
|
Definition
DNA hypomethylation: microsatelite instability, oncogene activation, loss of imprinting
X-chromosome inactivation
DNA Hypermethylation: silence tumor suppressor gene |
|
|
Term
| Familial Hypercholesterolemia |
|
Definition
more severe if homozygous
lots of cholesterol (shows up earlier)
xanthomas (deposits of cholesterol in skin and tendons) |
|
|
Term
Family adenomatous polyposis (FAP)
Apdenomatous polyposis coli (APC) |
|
Definition
Symptoms: benign adenomatous polyps in first two decades, one(+) polyp malignant
Inheritance: auto dom, APC (tumor supressor gene)
Biochemical: beta catenin activated w/o APC, more proliferative gene expression
Treat: remove colon |
|
|
Term
|
Definition
growth deficiency, brain malformation, short palpebral fissures, thin upper lip, smooth philtrum, behavior problems
tetratology related |
|
|
Term
|
Definition
Symptoms: mental retardation, large head, prominent jaw after puberty, large testes, autistic features
Inheritance: triplet nucleotide expansion of FMR1, normal transmitting males (carriers with normal pheno); 50-200 repeats prrmutation, >200 repeats mutant, mostly maternal transmission
Biochemical: loss of function of FMRP involved in mRNA transport in neural cells |
|
|
Term
|
Definition
Symptoms: vomiting and refusal to fee after first milk, liver disease, lethargy, cataracts, sepsis
Inheritance: autosomal recessive, locus heterogeneity, GALT mutation (Gln188Arg, missense, inactive protein); Duarte allele (Asn314Asp, 50% activity)
Biochemical: deficiency of galactose 1-P uridyltransferase (GALT), glactokinase (cataracts only) or epimerase; high levels of galactose is toxic
Treatment: galatactose-free diet (lactose-free formula) |
|
|
Term
HNCPP
Hereditary non-polyposis colon cancer
(Lynch syndrome) |
|
Definition
Symptoms:
Inheritance: auto dom, 5-10% CRC, 80% penetrance, late onset, mutant mismatch repair genes, LOH
Biochemical: microsatellite instability, increased rate of mutations |
|
|
Term
|
Definition
Hereditary neuropathy with liability to pressure palsies
Symptoms: episodic numbess, atrophy with minor trauma
Inheritance: deletion of PMP-22 |
|
|
Term
| Hardy-Weinburg Equilibrium |
|
Definition
|
|
Term
|
Definition
Symptoms: frequent bleeding, bleeding to joints
Inheritance: x-linked recessive, clotting factor VII gene, often inversion type mutation
Biochemical: minor symptoms with 5% activity, full disease <1% activity |
|
|
Term
|
Definition
Pro: high titer, large genome
Con: non-integrating, ? Toxicity
Target: CNS, cancer |
|
|
Term
|
Definition
failure of midface and forebrain to develop well
most common congenital brain defect
lots of causes, hedgehodge mutation |
|
|
Term
|
Definition
Symptoms: long/thin habitus, downward lens dislocation, thomboembolism, joints are tight
Inheritance: autosomal recessive with locus heterogeneity
Biochemical effect: deficiency/loss of cystathionine synthase (converts homocystein to cystathionine, uses pyridoxal phosphate cofactor)
results in excess homocysteine and impairs disulfide bridging of FBN1
Treatment: vitamin therapy and pyridoxine used as treatments, betaine (covert homocystein to methionine) |
|
|
Term
|
Definition
Symptoms: progressive abnormalities, involuntary movements, agression, apathy, psychosis, 15-18 yrs post-dx
Inheritance: autosomal dominant, late onset, expanded repeat in HTT gene coding region, few new mutations, 40-55 repeats = late onset, >60 = juvenile onset
Biochemical: Huntingtin protein accumulates in nucleus with gain of function affecting rate of neuron decay |
|
|
Term
| Indiana new born screening |
|
Definition
| PKu, galactosemia, maple syrup urine disease, homocystinuria, biotinidase deficiency, hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis, and sickle cell anemia |
|
|
Term
| Leber hereditary optic neuropathy (LHON) |
|
Definition
disease of mitochondria
results in blindness due to optic nerve degeneration |
|
|
Term
|
Definition
Pro: integrates, non-toxic
Con: insertional mutagenesis
Target: bone marrow, other stem cells, T cells |
|
|
Term
|
Definition
Symptoms: red-orange sand in diapers, hyperuricemia, self-mutilation, gout, kidney stones
Inheritance: x-linked recessive
Biochemical: deficiency of HPRT (part of purine salvage), buildup of (hypo)xanthine and uric acid
Treat: allopurinol (prevent uric acid build up) |
|
|
Term
| Maple syrup urine disease (MSUD) |
|
Definition
Symptoms: normal at birth, first week of life -> lethargy, weight loss, acidosis, hyperammonemia, sweet urine odor
Inheritance: autosomal recessive
Biochemical: deficiency of BCKA DH (6 gene complex), accumulation of BCAA and BCKA --> ketoacidosis and neurological toxicity
Treatment: diet low in leucine, regular monitor Leu, Iso, Val; liver transplant |
|
|
Term
|
Definition
tall/thin, large hands and long thin fingers
upward lens dislocation
dissecting aneurysms, valvular incompetence
autosomal dominant with pleiotropy and variable expressivity, heterogeneity
defect in Fibrillin-1 gene (glycoprotein of microfibrils in ECM)
25-35% de novo mutations
haploinsufficiency and dominant-negative effects
overactivity of TGF-beta from lack of FBN1 |
|
|
Term
|
Definition
Symptoms: progessive muscle wasting (begins in face), unable to relax after contract (myotonia), early cataracts
Inheritance: autosomal dominant, anticipation, DMPK gene (inc. repeats in 3' noncoding region), trans dominant RNA
Biochmical: extra repeats cause wtong splicing 9 of a chloride channel -> hyperexcitability of skeletal m., |
|
|
Term
|
Definition
| largest impact of single malformations |
|
|
Term
|
Definition
Symptoms: multiple fleshy tumors in skin, cafe-au-lait spots, lisch nodules,
Inheritance: autosomal dominant, variable expressivity, pleiotropic (affects many tissues), allelic heterogeneity, loss of heterogeneity |
|
|
Term
| Newborn Screening Criteria |
|
Definition
1. well defined and high population frequency
2. w/o treatment has high morbidity/mortality
3. treatment/intervention available
4. asymptomatic at early stages
5. rapid, inexpensive, specific, highly sensitive test
6. public health infrastructure |
|
|
Term
| Osteogenesis Imperfecta Type II |
|
Definition
autosomal dominant, mostly new mutations
brittle bones, large unmineralized skull
perinatal lethal |
|
|
Term
|
Definition
genetic imprinting
mental retardation, hypotonia, short stature, compulsive overeating, obesity
parental deletion with maternal imprint on chromosome 15 |
|
|
Term
|
Definition
Symptoms: mousy body odor/urine, hyperyphenylalnienemia, developmental delays, microcephaly, fair skin, eczema
Inheritance: autosomal recessive, allelic heterogeneity (likely compound heterozygotes), locus heterogeneity
Biochemical: deficiency of phenylalanine hydroxylase (converts phenylalanine to tyrosine, uses BH4 as cofactor); high Phe levels inhbits transport of neutral aa across BBB
Treatment: screening (onset by 6 months, has already effected mental development), dietary Phe restriction, lifetime |
|
|
Term
| Polycystic kidney disease |
|
Definition
Symptoms: bilateral kidney cysts, hypertension, blood in urine, kidney stones
Inheritance: autodomal dominant, late onset, mutations in PKD1, allelic heterogeneity, second hit needed |
|
|
Term
|
Definition
Pro: integrates, non-toxic
Con: insertional mutagenesis
Target: bone marrow, other stem cells, T cells |
|
|
Term
|
Definition
Symptoms: onset 6-18 months, slow head growth, loss of milestones, washing/wringing/squeezing hands
Inheritance: x-linked dominance, variable expressivity, most sporadic paternal mutation to MeCP2
Biochemical: loss of MeCP2 leads to inappropriate expression of genes |
|
|
Term
|
Definition
a sequence defect
U-shaped cleft palate and small mandible |
|
|
Term
|
Definition
| developmental regulatory gene |
|
|
Term
| Thiopurine methyltransferase (TPMT) |
|
Definition
| Metabolizes thoopurine class of chemotherapies |
|
|
Term
|
Definition
cleft lip and possible cleft palate and/or lip pits
reduced penetrance |
|
|
Term
|
Definition
variable expressive
white forelock |
|
|
Term
|
Definition
number of different alleles at same locus give same physical phenotype
most diseases |
|
|
Term
|
Definition
Phenomenon where there is progressively earlier onset and/or increased severity of disease with successive family generations
Ex: mytonic dystrophy |
|
|
Term
|
Definition
type of multiple birth defects
low frequency clustering of defects but no clear connection between them |
|
|
Term
| autosomal dominant disorders |
|
Definition
| Huntingon, Alzheimer, Neurofibromatosis, Marfan, Hypercholesterolemia, Myotonic dystrophy, PCKD, Achondroplasia |
|
|
Term
| autosomal recessive diseases |
|
Definition
| Cystic Fibrosis, congenital deafness, Tay-Sachs, Sickle cell, Phenyltonuria |
|
|
Term
| carrier frequency (recessive) |
|
Definition
|
|
Term
|
Definition
| 2 different mutant allele's at same locus |
|
|
Term
|
Definition
heart defects, hearing loos, eye abnormalities
"Blueberry muffine baby"
mother infected, pass to baby |
|
|
Term
|
Definition
| inbreeding, increased chances of getting autosomal recessive disease |
|
|
Term
|
Definition
type of single birth defect
mechanical stress to normal tissue
altered form like a dent in the skull |
|
|
Term
|
Definition
type of single birth defect
breakdown of normal tissues
necrosis, amputation by amniotic band |
|
|
Term
|
Definition
|
|
Term
|
Definition
type of single birth defect
abnormal developmetn of specific fetal tissue
ex: achondroplasia |
|
|
Term
|
Definition
when germ cells are made they pick up a couple mitochondria at random to make an oocyte
those mitochondria are then amplified
few selected, then multiplied greatly |
|
|
Term
|
Definition
one allele on and the other is off
certain genes from mother or father are turned off |
|
|
Term
|
Definition
gonad cells, multiple gametes can inherit mutation and pass along
parent unaffected with multiple affected offspring
ex: Neurofibromatosis 1 |
|
|
Term
|
Definition
| two different homologs from same parent |
|
|
Term
|
Definition
| cell whose mtDNA is different |
|
|
Term
|
Definition
| cell whose mtDNA is identical |
|
|
Term
|
Definition
| two copies of same homolog from same parent |
|
|
Term
|
Definition
| Huntington, Alzheimer, Breast cancer |
|
|
Term
|
Definition
mutations at different loci give same clinical phenotypes
ex: Ehlers Danlos Syndrome |
|
|
Term
|
Definition
skewed x-inactivation
one X inactivated early in embryo
same X inactivated in descendant cells |
|
|
Term
|
Definition
type of single birth defect
disorder of tissue development
usually during first trimester |
|
|
Term
|
Definition
| individual or tissue can have two different sets of genes in their cells |
|
|
Term
|
Definition
not all individuals with disease present with clinical symptoms
#affected/totalwithmutation |
|
|
Term
|
Definition
type of multiple birth defects
single anomaly that cascades and causes a bunch of other anomalies |
|
|
Term
|
Definition
| phenotypic expression of an allele related to the chromosomal sex of the individual |
|
|
Term
|
Definition
most cells normal, but one line of offspring of cells has mutation
non-inheritable effects |
|
|
Term
|
Definition
type of multiple birth defects
recognized pattern of defects from a specific genetic etiology
ex: Down syndrome |
|
|
Term
|
Definition
study of birth defects and their causes
several factors determine a specific sitmulus's tetratologenicity |
|
|
Term
|
Definition
| if enough mitochondria in a cell have mutant alleles, then the cell will be symptomatic |
|
|
Term
|
Definition
both homologs of a chromosome pair come from the same parent
nondisjunction during meiosis |
|
|
Term
|
Definition
the expression of the disease is variable between individuals
common to genes that affect multiple systems
Ex: Waardenburg Syndome |
|
|
Term
|
Definition
| seen more often in females |
|
|
Term
|
Definition
more often found in males
ex: color blindness |
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