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72 Cards in this Set
- Front
- Back
Mutation at 17q11.2 |
NF-1 |
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Mutation in a tumor suppresor that down-regulates Ras in the MAP Kinase pathway |
Neurofibromin 1, NF-1 |
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Mutation on Merline gene, at 22q12 |
NF-2 |
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Mutation on gene that codres for a tumor suppressor protein in Schwann cells |
NF-2 |
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Mutation at 15q21.1 |
FBN-1 gene Marfan's |
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Mutation in fibrillin gene |
FBN-1 Marfan |
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Gender effect on threshold example |
Pyloric stenosis - Males more commonly affected |
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Cleft lip/palate, congenital heart defects |
examples of congenital malformations |
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Open neural tube defects (ONTDs) |
Congenital malformations example |
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Spina bifida and anencephaly |
Multifactoral condition - congenital malformation Env (folic acid) + genetic risk |
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Coronary artery disease |
adult onset multifactorial disease example |
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Thrombosis |
adult onset multifactoral disease example |
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Mutation in this gene increases levels of homocysteine (correlated with risk factor for cardiovascular disease) |
MTHFR |
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Prothrombin 20210A mutation Factor V Leiden |
Increases risk for VTE (venous thromboembolism) |
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Protein S, C, or antithrombin III deficiency |
Genetics factors for thrombosis |
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Surgery/trauma Cancer Chronic conditions (diabetes, obesity, hypertension, high cholesterol) Smoking Prolonged inactivity Hormone: pregnancy, oral contraceptives, estrogen therapy |
Environmental factors for thrombosis |
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BRCA1 BRCA2 p53 gene mutations |
Breast cancer genetic risk factors |
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Nulliparity Early age of menses Late age of menopause |
Breast cancer environmental risk factors |
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Mutations in APC, MYH, and DNA repair genes |
Colorectal cancer genetic risk factors |
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Low fiber diet and lack of exercise |
Colorectal cancer environmental risk factrs |
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HLA class II alleles (DR3 and DR4) |
Type I diabetes (IDDM) |
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Some families affected by rare, AD genes, most families exhibit multifactoral inheritance patterns |
Type II diabetes (NIDDM) |
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Schizophrenia (H=70%) and bipolar affective disorder (H=94%) |
Heritable psychiatric disorders that are multifactorial |
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Have the largest impact on specific families (rarer) |
Mendelian disorders |
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Have the largest impact on population as a whole (more common) |
multifactorial disorders |
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Mutation on FMRI gene on Xq27.3 |
Fragile X Syndrome |
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Fragile X (FRAXA) Myotonic dystrophy (MD) Friedreich ataxia (FRDA) Fragile X "E" MR (FRAXE) SCA8, SCA12 |
Examples of trinucleotide repeat in non-coding regions (introns, promoters, etc.) |
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Most common form of inherited cognitive impairment |
Fragile X syndrome (FMR1 gene - Xq27.3) |
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Macrocephaly Large ear Marco-orchidism Echolalia Perseverative speech Gaze avoidance 2-6% diagnosed with autism |
Fragile X Syndrome (FMR1 gene - Xq27.3)
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Clinical description of genetic anticipation |
Sherman paradox - Fragile X Increased especially when passed through a female |
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CGG repeat triplet sequence normally present in the promoter (5' end) of FMR1 gene |
Fragile X |
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>200 repeats of CGG |
Result in methylation of promoter and inability to express the FMR1 mRNA/protein Fragile X |
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Premutation |
Expansion of repeat, but not significant enough to cause phenotype Also unstable - may expand to full mutation in next gen. |
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Normal: 0-44 Intermediate: 44-55 Premutation: 55-200 Mutation: >200 CCG repeates |
Fragile X syndrome Stable when passed through males Unstable and may expand when passed from females |
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POI/POF, fragile X-associated tremor ataxia (FXTAS) |
Due to excess mRNA Premutation: 55-200 CCG repeats Fragile X |
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CTG expansion in the 3'UTR of the DMPK gene |
Myotonic Dystrophy (MD) DMPK gene codes for myotonin protein kinase |
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35-49 CRG repeaset |
MD premutation, no clinical signs |
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Can expand after maternal transmission, contract after paternal |
CTG premutation (MD) |
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Cataracts, mild myotonia |
Mild MD 50 - 150 CCG repeats Age of onset: 20-70 |
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Weakness, myotonia, cataracts, balding, cardiac arrhythmia, others |
Classic MD 100-1000 CCG repeats Age of onset: 10-30 |
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Infantile hypotonia respiratory deficits cognitive impairment |
Congenital MD >2000 CCG repeats Birth-10 |
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GAA triplet repeat expansion in intron of Frataxin gene (>200) |
Friedrich's ataxia (FRDA) AR disease that causes progressive neurological deterioration |
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Low expression of frataxin results in mitochondrial dysfunction due to iron accumulation |
FRDA |
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Cerebellar involvement (ataxia, dysarthria, titubation, scoliosis, pes cavus) Hearing loss, cardiac, endocrine |
FRDA |
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CAG polyglutamine disease |
Trinucleotide repeat in coding region Huntington disease |
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Full penetrance: 40 + CAG repeats |
Huntington's disease |
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The telomeres get shorter than the general population and correlate with increased risk of ______ cancer at earlier age |
BRCA1/BRCA2 breast |
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Mouse - both maternal pronuclei |
embryo develops placenta is poor |
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Mouse - both paternal pronuclei |
placental develops embryo is poor |
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All chromosomes are derived from a single parents |
Uniparental diploidy |
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Human - both maternal pronuclei in the same germ cells |
ovarian teratomas or dermoid tumors |
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Human - both paternal pronuclei are only (or primarily) paternal in origin |
Complete mole (46) with ONLY paternal chromosomes - risk of malignancy Partial mole (triploid, 69) fetal parts can be seen, no malignancy |
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-neonatal hypotonia -poor feeding , failure to thrive up to age 2 -short stature, small hands and feet, micro-penis, hypogonadism -various degrees of cognitive disability -microcephaly -obesity -sometimes albinism -lack of ability to regurgitate-great with puzzles |
Prader-Willi |
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progressive microcephaly, - severe cognitive delay, lack of speech onset- gait ataxia, at one time referred to as the “happy puppet” syndrome- abnormal EEG , seizures can occur usually by age 3- sometimes also have albinism |
Angelman Syndrome |
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Non functional paternal alleles at 15q11 |
Prader-willi |
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Non functional paternal alleles at 15q11 |
Angelman |
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Gene mutations in the maternally derived allele of UBE3A |
Angelman |
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Paternal uniparental disomy at 11p15 |
Results in over-expression of the insulin like growth factor 2 (IGF2) Beckwith-Weidemann Syndrome |
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High risk for embryonal tumors (such as Wilm's tumor and/or heptoblastoma) Neonatal hypoglycedmia Macrosomia posterior helical ear pit and creases abdominal wall defects (omphalocele, diastasis recti, or umblicial hernia) |
Beckwith-Weidemann |
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Intrauterine growth retardation (IUGR), post natal short stature, hemi-hypotrophy, broad forehead with normal head circumfrance, narrow chin, 5th finger clinodactyly |
Russell Silver Syndrome (RSS) |
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Maternal uniparent disomy for chromosome 7 |
Russell Silver Syndrome |
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Hypomethylation of paternal chromsome 11p15.5 |
decreased expression of IGF2 gene Russell Silver Syndrome |
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Multiple endocrine neoplasia (MEN2) Pheochromocytomas Parathyroid adenoma/hyperplasia Mucosal neuromas of lips, tongue Marfanoid habitus |
RET proto-oncogene
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The Philadelphia chromosome translocation involving 9 and 22 - with breakpoints in the proto-oncogene ABL (9) and BCR (22) genes |
Results in a fused gene that changes function of ABL gene CML and ALL |
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Hereditary retinoblastoma |
Hereditary cancer - 90 risk to heterozygotes |
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Breast, ovarian, male breast, pancreatic, prostate Caretaker genes: involved in DNA repair, response to double stranded DNA breaks |
Hereditary breast and ovarian cancer syndrome BRCA1 AND BRCA2 |
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Colorectal, small bowel, stomach, pancreas, thyroid, CNS, liver 100-1000s of adenomas lining the colon and rectum |
Familial adenomatous polyposis (FAP) |
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CHRPE spots Desmoid tumors Osteomas Epidermoid cysts or fibromas |
FAP |
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Colonoscopy/sigmoidoscopy every 1-2 years starting AD inheritance APC gene (tumor suppressor) |
FAP |
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Colon, endometrium, stomach, ovary, other (hepatobiliary tract, urinary tract, small bowel, brain/central nervous system) 50% risk of second cancer within 15 years |
Lynch syndrome (HNPCC) |
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Mismatch repair genes (caretakers): MLH1, MSH2, PMS2, MSH6 MMR GENE |
Lynch
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MEN2A and MEN2B RET |
Heritable proto-oncogenes |