Term
|
Definition
| About _____(#) human diseases are known to cocur from changes in a single gene on an ________. |
|
|
Term
single osteopenia 5/100,000 5/100,000 dominant I COL1A1 COL1A2 |
|
Definition
| Osteogenesis Imperfecta is a ______ gene disorder that characteristically shows a decrease in bone mass known as __________. The frequency of this disease is ________, and the carrier frequency is __________. It is an autosomal _______ disorder of type _ procollagen. The mutated genes are ______ and ______. |
|
|
Term
|
Definition
| The recurrance risk of osteogenesis imperfecta is __%. |
|
|
Term
recessive CFTR 1/3000 1/27 25% chloride |
|
Definition
| Cystic fibrosis is an autosomal _________ disorder involving the mutation of the ____ gene on chromosome 7. The prevalence is ______ in caucasions and the carrier frequency is ____. The recurrence rick is __%. The ________ ion transporter defect produces over-thick mucus. |
|
|
Term
|
Definition
| _________ are non-sex-linked chromosomes and occur in pairs. A single gene occurs at a specific _____ on a chromosome. |
|
|
Term
|
Definition
| A mendelian trait= a _________ trait. |
|
|
Term
|
Definition
| Members of a gene pair that are not identical are _______. |
|
|
Term
|
Definition
| ___________ __________ means that genes at different loci are transmitted independently. |
|
|
Term
|
Definition
| _____ individuals are affected by some dominant disease, however each specific disease is rare. |
|
|
Term
heterozygotes 50% independent |
|
Definition
| Inheritance of an autosomal dominant disorder usually affects ____________. __% of children will be affected and the risk is ___________ of gender of the child. |
|
|
Term
|
Definition
True or False? Tather to son transmission occurs in autosomal dominant disorcers and in autosomal recessive disorders. |
|
|
Term
|
Definition
| The recurrence risk of an autosomal dominant disorder is __% and the recurrance risk of an autosomal recessive disorder is __%. |
|
|
Term
|
Definition
| Generations are usually skipped in autosomal _________ disorders and they are not usually skipped in autosomal ________ disorders. |
|
|
Term
|
Definition
| Carriers of autosomal recessive diseases are frequent commonly ____ to ____, and these diseases are normally inherited by progeny of two _____________. |
|
|
Term
|
Definition
| _____________ greatly increases the risk of recessive diseases. |
|
|
Term
Product (multiply) Sum (addition) |
|
Definition
| The probability that two independt events will BOTH occur is the ___ of the individual probablities. The probability that one or the other of two independent events will occur is the ___ of the individual probablities. |
|
|
Term
phenotype gene frequency genotype frequency |
|
Definition
| _________ is the physical manifestation of a certain genotype influenced by environmental factors. ____ _____ is the probability of occurence of a specific allele in the population (A or a). ____ ____ is the probablity of each genotype in population (AA, Aa, aa, etc...). |
|
|
Term
homozygote (p^2 or q^2) Hardy Weinburg p^2 + 2pq + q^2=1 p (dominant), q (recessive) |
|
Definition
| The frequency of a gene allele is the square root of the __________ frequency. |
|
|
Term
2% q=(1/2500)^1/2 q=1/50 (2%) 4% q + q= 1/25 |
|
Definition
| If the frequency of CF is 1/2500, then of all the CFTR genes in the caucasion population _% are a mutated form causing CF. Thus, the frequency of CF carrier genotype, Aa or aA is _%. |
|
|
Term
|
Definition
| ________ cell mutation are heritable while _______ cell mutation can cause cancer, but are not inherited. Copies of a gene on each of the two homologous chromosomes are called _______. |
|
|
Term
|
Definition
| A locus is ____________ if many alleles are represented at greater than 1% frequency in the population. |
|
|
Term
1- over-expression of a gene product 2- expression of gene product in an inappropriate (non-producing) cell context 3- expression of a gene with an altered fxn Dominant |
|
Definition
Gain of function mutation can cause 3 things: These gain of function mutation typically produce ________ disorders. |
|
|
Term
active protein Homozygotes heterozygote |
|
Definition
| Loss of function mutations prevent the production of ______ _______. __________ lack any normal gene product, hence are more strongly affected than any ____________ for both recessive and dominant disorders. |
|
|
Term
recessive Pseudo-dominant haploinsufficiency |
|
Definition
| A mutation is _________ when there is no detectable pathological effect of the activity loss or of the presence of the mutant protein. ______-________ mutations result when insufficient normal product (activity) is present for non-pathological fxn. This effect is known as ______________. |
|
|
Term
negative inhibits multi-protein-complex Osteogenesis imperfecta |
|
Definition
| Dominant ________ mutations result when the mutant protein ________ the function of the normal protein. These usually affect a protein in a _____-______ _______. An example is __________ _______, which results fromt he mutation in one collagen I chain that cause abnormally assembled collagen triple helices. |
|
|
Term
Homozygotes heterozygotes gene dosage Achondroplasia |
|
Definition
| ___________ of autosomal dominant diseases are often more affected than _____________ due to increased _____ _______. An example of this is ______________. |
|
|
Term
dominant gene dosage spontaneous FGFR3 (fibroblast growth factor recepter) |
|
Definition
| Achondroplasia is an autosomal _______ disorder where the heterosygote is less affected that the homozygote due to lower ____ ______. 7 or 8 achondroplasia cases arise from ___________ mutations leading to constitutive activation of the _____ which restrains chondrocyte proliferation and causes skeletal abnormalities. |
|
|
Term
enzymes carriers transporters |
|
Definition
| Recessive mutations are usually negative and affect proteins that act in series (alone), 3 examples of these proteins: |
|
|
Term
1- signaling system components 2- componenets of other cascade processes (clotting...) 3- structural proteins 4- proteins in multi-protein complexes, including transcription factors. |
|
Definition
Dominant mutations are positive or negative and usually affect proteins that act in concert with other proteins such as? (4) |
|
|
Term
1- variable expression 2- pleiotropy 3- variable penetrance 4- germ cell mosaicism |
|
Definition
| Multi-organ effects are referred to as: (4) |
|
|
Term
Pleiotropy lungs pancreas digestive system sperm production |
|
Definition
| CF exhibits __________ because a single mutant gene has pathological effects of multiple parts of the body: _____, ________, _________, and _____ __________. |
|
|
Term
|
Definition
| The most common cause of CF is a mutation in the _____ gene, and this particular form of CF leads to severe pancreatic insufficiency. |
|
|
Term
Marfan arachnodactyly dominant variable 10-30 FBN1 (fibrillin-1) 550 |
|
Definition
| ______ syndrome is another pleiotropic disease that is chacacterized by long, thin extremities with loose joints and ______________. This is an autosomal ________ with ________ penetrance. The prevalene is __-__ per 100,000 and these are within racial and ethnic groups. This disease is a result of a mutation of the ____ gene, and over ___ different mutations have been identified. |
|
|
Term
|
Definition
| Dominant _________ mutations disrupt the function of the remaining normal protein. |
|
|
Term
|
Definition
| This disease has variable espression than can result in pigmented skin lesions, inheritance is autosomal dominant, and the prevalence is 25/100,000. |
|
|
Term
penetrance dominant 1/20,000 40% 60% |
|
Definition
| Retinoblastoma exhibits reduced __________, meaning that not all individuals who inherit are afected. It is an autosomal ________ and it's prevalence is _______. __% of cases are inherited and __% of cases are spontaneous. |
|
|
Term
|
Definition
| Reduced penetrance occurs because of the "two-hit" mechanism, meaning a second ________ is required to express disease. |
|
|
Term
NF1 neurofibromin ras GTPase |
|
Definition
| In a patient with neurofibromatosis, you know that the mutation is in the ___ gene on chromosome 17. This gene encodes a tumor suppressor called _____________. Under normal circumstances, this tumor suppressor modulates signaling in the ___ ______ pathway. |
|
|
Term
Rb pRb E2F TF (transcription factor) CDKs. |
|
Definition
| Retinoblastoma is causes by a mutation of the __ gene on chromosome 13. The protein encoded in this gene ___ is a tumor suppressor that inhibits ___ __, which is required for cell division and is activated by ____. |
|
|
Term
Anticipation triplet dominant |
|
Definition
| ___________ describes an increased severity in successive generations. In muscular dystrophy this is related to increasing _______ repeat size in successive generations. This type of MD and it is inherited in an autosomal ________ fashion. |
|
|
Term
|
Definition
| Spontaneous (new) mutations are usually ________ mutation and are a common source of autosomal ________ traits. Examples are achondroplasia (7 of 8 cases) and neurofibromatosis(30-50% of cases). The recurrence risk is ______(Low? High?). |
|
|
Term
Neurofibromatosis Osteogenesis imperfecta |
|
Definition
Classic cases of variable expression and locus heterogeneity include: (2) These types of diseases reduce natural selection against the disease. |
|
|
Term
|
Definition
| Two classic cases of Pleiotropy are? |
|
|
Term
|
Definition
Familial alzheimer's and inherited cancers are examples of ___-_________ penetrance, and onset is delayed into adulthood. |
|
|
Term
|
Definition
| _________ with repeat expansion is pressent when the severity of the disorder increases in younger generation. |
|
|
Term
|
Definition
| ________ _________ may be present when 2 children are affected without family history. |
|
|
Term
random mosaics maternally paternally |
|
Definition
| X-inactivation is ______, hence females are _______, half of cells X-chromosomes are ___________ derived, and half are __________ derived. So...if one X is diseased...50% of cells will be affected. |
|
|
Term
epigenetic Chromatin epigenetic Xist |
|
Definition
X-inactivation is fixed in a cell ine and is _________, innactivation affects _________ structure, not DNA sequence, hence it is _______ (same as first blank). Inactivation involves a special RNA, ____ RNA, expressed by the chromosome to be inactivated. |
|
|
Term
|
Definition
| X-inactivation occurs early in development: _=_ days after fertilization. |
|
|
Term
Turner syndrome (no X-inactivation b/c only one X) Klinefelter syndrom (XXY) X-trisomy (XXX) |
|
Definition
| Three examples of X-inactivation in Chromosome disorders? |
|
|
Term
|
Definition
______ carriers are normally unaffected by X-linked recessive disorders. Some are affected however when there is ____ in X-inactivation. |
|
|
Term
|
Definition
| A preponderance of X-inactivation of the X-chromosome carrying the ______ allele will increase the dosage of the disease allele. |
|
|
Term
|
Definition
| X-linked recessive inheritance predominantly affects ____ progeny. THis progeny inherit the disease genes from their mother or father? |
|
|
Term
|
Definition
| Generations are often skipped in X-linked recessive disorders because __% of females in an inheritance line are carriers and __% of males inherit the disease allele. |
|
|
Term
male daughters heterozygote |
|
Definition
| In X-linked recessive inheritance, _____progeny of an affected father are not affected, but all _________ are carriers. Daughters of an affected father if the mother is a ____________ for the disease. |
|
|
Term
|
Definition
| Factor ___ is an antihemophilic facor that is deficient in Hemophilia A. This factor regulares the activation of factor __ by proteases generated in the intrinsic coagulation pathway. |
|
|
Term
|
Definition
| Male-to-Male transmission is not seen in X-linked ________ inheritance. Daughters of affected fathers will always be ________. __% of sons and daughters of affected mothers are affected. |
|
|
Term
|
Definition
Twice as many ____ are affected as ____ in the whole population of X-linked dominant inheritance. |
|
|
Term
|
Definition
The _______ paradox: Daughters of normal transmitting males (NTM) are not affected, BUT unaffected daughters of NTMs often produce affected sons (grandsons of NTM) |
|
|
Term
trisomy 15 Increased Reduced |
|
Definition
In complete X-inactivation causes disease (_______ disorders). About __% of genes remain active in 'inactive' X-chromosome, and an extra X chromosome causes increased dosage of these active genes. _________ gene dosage accounts for pathologies of Kilinefelter and XXX trisomy syndromes. _______ gene dosage accounts for pathologies of Turner's Syndroms. |
|
|
Term
|
Definition
| Mitochondrial diseases are rare and __________ derived. |
|
|
Term
|
Definition
| Most __________ disorders are loss of function mutations while gain of function mutation usually produce ________ disorders. |
|
|
Term
1-point mutations (single base change) 2- insertions and deletions (also called frameshift mutations) 3- Triplet repeat expansion (a form of microsatellite expansion) 4- gene rearrangements |
|
Definition
| There are four main types of mutations commonly associated with single gene disorders: |
|
|
Term
transitions transversions missense nonsense |
|
Definition
Point mutations can result in: 1________ (pu-->pu or pyr-->pyr) 2_______ (pu<-->pyr) 3________(amino acid change) 4_________(STOP codon) |
|
|
Term
mutations 1-most DNA damage is random 2- most DNA damage is repaired 3-Most DNA repair is random |
|
Definition
Cancer is a multi-factorial disease because multiple ________ are required to express the disease. Cancer is statistical because: (3) |
|
|
Term
1- recombination (unequal crossover) 2- DNA sequence transposition 3-DNA sequence expansion 4- Insertion of foreign DNA |
|
Definition
Large-scale genome changes can occur by four mechanisms: |
|
|
Term
1- replicaiton errors 2- spontaneous base changes 3- damaged bases 4- errors in repair |
|
Definition
| Small scale genome changes can occur by four mechanisms: |
|
|
Term
chromosome abnormalities crossover events gene conversion transposition viral gene integration sequence expansion |
|
Definition
Types of Gene rearrangements include: (6) |
|
|
Term
all parent's spontaneously meiosis may not (depending on the spread of the mutation in the germ line) |
|
Definition
Gene rearrangements are that are present in ___ cells are inherited and they occured in the ____ germ line. All children will be at equal risk if if germ line rearrangements are inherited. Germ line rearrangements may also arise _________ in the germ line of one parent, most commonly during ______. All children (may/may not?) by at equal risk? |
|
|
Term
spontaneous transformation inherited |
|
Definition
Somatic gene rearrangements are ________. Viral gene integration may cause cell _________ contributing to cancer. These genes are not generally __________. |
|
|
Term
Gene duplication mobile element |
|
Definition
| Three main types of gene rearrangement by expantion include ____ ________ which causes increased gene dosage, triplet repeat expansion (huntington's), and _______ ________ insertion like SINES and Alu repeats. |
|
|
Term
homologous loss gain preservation |
|
Definition
| Unequal crossover events may occur between _______, but not identical, sequences and cause gene rearrangements. These can cause ____, ____ or ______ of function. |
|
|
Term
|
Definition
| Sister chromatid exchanges will cause gene changes in a ________ daughter cell. These changes are propagated by additional cell divisions, possible causing _____ growth. |
|
|
Term
Integrase Reverse transcriptase |
|
Definition
| ______ is the enzyme that helps viral DNA, and DNA from the retrovirus mechanism integrate into the host DNA. ______ ________ is the enzyme that makes the retrovirus mechanism possible. |
|
|
Term
chemical ionizing radiation |
|
Definition
| DNA damage as a result of environment can be caused by ________ carcinogens, _______ ________, UV light, and oxidizing agents. |
|
|
Term
|
Definition
| Spontaneous DNA damage may be induced by replication erros, _____ (apurinic sites) or _________ (base change; most common). |
|
|
Term
|
Definition
| ______ cancer is currently the most prevalent cancer in women. |
|
|
Term
|
Definition
| __% of cancers are 'caused' strictly by environmetnal factors, and virtually all have an environmental component. |
|
|
Term
2-Acetylaminofluorene dyestuffs, pigments |
|
Definition
| Benzo[a]pyrene is a potent environmental carcinogen that is common in fossil fuels, and tobacco products. __________ is another one that is common in fossil fuel emissions and tobacco products as well. N-Methyl-4-aminoazobenzene however is common in _________, _________. |
|
|
Term
cytochrome P450 monooxygenases Hydrolase |
|
Definition
Aromatic procarcinogens are activated to ultimate carcinogens by ___________ __ ________. Oxigenases add oxygen to form reactive enzymes and hydroases convert epoxides to hydroxyl groups, inactivate epoxide. ______ deficiency predisposes to cancer. |
|
|
Term
|
Definition
| In 2004 Cancer was the #2 leading cause of deaths with __% of all deaths. Heart disease was number 1 with 27.2% |
|
|
Term
|
Definition
Estimated US cancer deaths in men: % Lung and bronchus prostate colon and rectum pancreas |
|
|
Term
|
Definition
Estimated US cancer deaths in women: % lung and bronchus breast colon and rectum pancreas ovary |
|
|
Term
EVERYONE men: 1/2 women 1/3 |
|
Definition
| ________ is at a high lifetime risk of developing cancer. |
|
|
Term
|
Definition
| Survival rates are ______ for most cancers, but not for _____ cancer. |
|
|
Term
Unwanted cell growth Invasiveness Metastatic |
|
Definition
| Three characteristics of cancer? (3) |
|
|
Term
|
Definition
| Primary tumors are not _____- the problem is ______, where stem cells enter the organ and develop into a secondary tumor. _____ assist escape and relocation of these cells. |
|
|
Term
|
Definition
Proteases and ______ factors are targets of cancer therapies. |
|
|
Term
CancersCancers Lethality greater than 1 kg |
|
Definition
| ____ arise from tumors that acquire the ability to invade through surrounding normal tissue. _____ results from the ability to destroy other tissues through invasion (Avg. tumor mass at death is ____). |
|
|
Term
heterogenous oncogenes tumor suppressor |
|
Definition
Cancer is a ________ disease because there are as many tumor types as cell types in the body. All tumor types result from defects in a subset of genes called ______ and _______ genes. |
|
|
Term
|
Definition
| Cancer is a disease of the ____ causing loss of __________ control. |
|
|
Term
|
Definition
| Some single gene defects predispose to cancer, but cancer requires ________ ________ mutations. |
|
|
Term
|
Definition
| Most mutated cancer genes arise spontaneously, BUT inheriting a defective "cancer gene" greatly increases the risk. One example is the ____ gene defect in colon cancer (0.5% is inherited), and another is the ______ gene in retinoblastoma. |
|
|
Term
|
Definition
| Chromosome loss followed by duplication of remaining chromosome is called _____ of _______. |
|
|
Term
|
Definition
Two classes of genes that are mutated in cancer: Genes that control cell ______ Genes that control the rate of ______ |
|
|
Term
tumor suppressor (apply "brakes" to cell cycle progression or promote apoptosis) oncogene (apply "accelerator" to cell growth or inhibit cell apoptosis) Caretaker |
|
Definition
Genes that control cell proliferation? Gatekeeper _____ _______ and _______ Genes that control the mutation rate? _______ tumor suppressors |
|
|
Term
|
Definition
| Mutation of the second gatekeeper allele is ___ ______ for tumor initiation in inherited cancers such as retinoblastoma. |
|
|
