Patho Exam 2 Flashcards
Penetrance
The precentage of individuals with the specific genotype who also exibit the expected phenotype.
Expressivity
The extent of variation in phenotype associated with a particular genotype. Ex) Neurofibromatosis
Proband
The first member of the family to be diagnosed
Euploid
Cells that have a multiple of 23 chromosomes. Most normal somatic cells are euploid.
Haploid
Gametes contain only one half of each chromosome pair, giving them a total of 23 chromosomes.
Diploid
All 46 chromosomes occur in pairs meaning that there are 23 pairs in each somatic cell.
Polyploigy
A cell which has more than 46 chromosomes. Some liver, bronchial and epoithelial cells are normally polyploidy. Must contain a multiple of 23 chromosomes. Eg 46 nor 93
Aneuploidy
Cells that do not contain a multiple of 23 chromosomes, usually the result of NONDISJUNCTION. Ex. Trisomy or Momosomy
Trisomy
Cells that contain three copies of one chromosome. Ex. Down Syndrome (Trisomy 21)
Partial trisomy
Only an extra portion of a chromosome is present in each cell. Consequences are less severe
Monosomy
Cells that contain one copy of a given chromosome. Monosomy of any cell is lethal.
Disjunction
When homolougus chromosomes separate normally during cellular devision.
Nondisjunction
When homologous chromosomes or sister chromatids fail to separate normally during either meiosis or meitosis.
Chromosomal mosaics
Individuals who have Trisomies occuring in some cells but not others. Occurs when nondisjunction occurs in one embryotic and not the others.
Composition of chromatin
Deoxyribose, bases and phosphate
Function of DNA polymerase
Adds bases to the growing 3’ of a DNA molecule during replicaion. “DNA Builds”:
Function of RNA polymerase
Pulls a portion of the DNA appart during transcription.
Autosomal Recessive characteristics of pedigree
Disease skips generations, is found in siblings, is eausal to both males and females.
Autosomal Dominant characteristics of pedigree
Disease is found in every genertion, effects nearly 50% of offspring, and is equal in males and females.
What are the two important sites on tRNA
The anticodon and the amino acid binding site.
Polyploidy occurs norally in which tissues
The Liver, Bronchial tissue and Epithelial cells.
Anuploidy occurs most frequently on which chromosomes?
13, 18 and 21
Fragile X Syndrome
A Trinucleotide dissorder where the CGG codon on the X chromosome is repeated nearly 200 times. It is the most prominent cause of MR. More common in males than females. Manifested by MR, Speech alterations, increased head circumfrence and joint hyperflexibility.
Robertson translocation
When the long arms of two chromosomes fuse at the centomere creating one large chromosome. The short arms fall away and there is no loss of genetic material. The carrier will have no phenotype however the offspring may be affected. It is limited to chromosomes 13, 14, 15, 21 and 22.
Down Syndrome
Cuaused by trisomy 21. Occurs in 1:800 live births. Low IQ, Distinct facial features, short stature, poor muscle tone, predisposition to heart murmers, lukemia and alzheimers.
Turner syndrome
Caused by a having only a single X chromosome. Affects only women. Characterized by short stature, female genitalia abnormalities, webbed neck, shield like chest, underdeveloped breasts and imperfectly developed ovaries
Klinefelter syndrome
Caused by having atleast two X chromosomes and a Y. Chatracterized by having a male appearance, usually sterile, breast development, long limbs, tall stature and small testes.
Cri du chat syndrome
Caused by the deletion of part of the short arm of chromosome 5. Characterized by “cry of the cat” distinctive cry, low birth weight, severe mental retardation, small head size, heart defects, distict facial appearance.
Huntington disease
An autosomal dominant disease. Charcterized by progressive dementia and uncontrolled movements of the limb. (Huntingto’s Chorea “Greek for dance”)
Cystic fibrosis
An autosomal recessive disease found in 1:2500 white births. Causes the formation of chloride channels leading to dehydration and thick secretions.
Neurofibromatosis
A.K.A. Von Recklinghausen disease. Abnormal tumor supression gene. Characterization varies widely from cafe‚ au lait spots, malignant tumors, scholiosis, seizures, gliomas, hypertension, learning disabilities and neuromas.
Hemophilia
An X linked recessive dissorder which impairs blood clotting.
Duchenne muscular dystrophy
X linked recessive disease. Caused by deleted portions of the DMD gene due to frameshift mutations. Characterized by progressive muscle deterioration, death caused by cardiac and respiratory failure.
Progeny
Offspring
Chromosomes
A single linear DNA sequence that is folded into a compact structure.
Gene
A segment of DNA sequence that codes for the synthesis of a singal protein
Allele
An alternative form of a gene in a specific location on a specific chromosome
Gamete
Sperm and egg cells
Homozygous
When the two gene pairs are identical at a locus.
Heterozygous
When the two gene pairs are different at a locus.
Dominant traits
The gene who’s effects are observable.
Recessive traits
The gene who’s effects are hidden.
Pedigree chart
A tool in the analysis of inheritance. It summarizes the family relationships and shows which members are affected by a genetic disease.
Polygenic Inheritance
Assumes multiple genes cause the disease but no environmental factors.
Relative Risk
Compare the risk of contracting a disease by people with the risk factor to those who do not have the risk factor. Ex) British physicians and lung cancer from smoking IR Risk Factor/ IR Non Risk Factor = Relative Risk
Threshold of Liability
The point at which environmental factors tip the scale and a person develops a disease.
Recurrence Risk
The likelihood that a trait or disorder present in one family member will occur again in other family members in the same or subsequent generations
Empiric Risk
Calculated over a large population. Populations can be matched to the patients own
- Socioeconomic class
- Ethnicity
- Geographic location
- Lifestyle
- Must be interpreted as an average estimate rather that a precise probability
Incidence Rate
The number of new cases of a disease reported during a specific timeframe. Ex If there are 1,000 non diseased people and 30 people contract the disease over 3 years then the incidence rate is 10 cases/ 1000 person year
Prevalence Rate
The proportion of the population affected by the disease at a given time. It is both new and old cases. Ex) HIV the incidence rate is high in Africa however people are living for a long time with the disease, so PR is up.
Genetic factors of Coronary Artery Disease
- There are more affected relatives.
- Affected relatives are female rather than male.
- Age of onset younger than 55 years.
- 2-7 times more likely to have heart disease in individual with positive family history.
Familial Hypercholesterolemia
Autosomal dominant disease that does not spare any racial or ethnic groups. It is a single gene disorder on the LDL receptor gene. Reduces the number of available LDL receptors which limits LDL absorption and increases serum LDL levels
LDL Receptor Mutations Class 1
Heterozygous produce only ½ of LDL receptors
LDL Receptor Mutations Class 2
Production of altered LDL receptor
LDL Receptor Mutations Class 3
LDL receptor cannot bind to LDL
LDL Receptor Mutations Class 4
Receptors do not migrate to clarathin coated pits
LDL Receptor Mutations Class 5
Receptor cannot dissociate from LDL
Mutation of ACE gene which commonly causes Essential HTN
A deletion or insertion of intron 16
Alpha Adducin
Research topic for HTN. Involved in regulating sodium reabsorption in the proximal tubule
BRCA 1
- Chromosome 17
- Tumor suppressor gene.
- Transcription and DNA repair.
- BRCA1 mutations can increase the risk of ovarian cancer among women (20-50% life-time risk
BRCA 2
- Chromosome 13
- Tumor suppressor gene.
- BRCA2 mutations also confer an increased risk of ovarian cancer (10-20% life-time prevalence).
- 6% males who have mutant BRCA2 develop breast cancer.
- Moderate increased risk of prostate cancers.
- Is a 100% increase in risk over the general male population.
Familial Adenomatous Polyposis
- Caused by inactivation of Adenomatous Polyposis Coli
- APC is on chromosome 5
- APC is a tumor suppressor gene
- They effect cell adhesion and transcription factors
Hereditary Non polyposis Colorectal Cancer
- Caused by mutations of 6 genes
- Cause a decrease in DNA repair
- Cause an increase in onca genes
BMI Formula
BMI = KG/ Meters Squared
APC
Adenomatous Polyposis Coli
- Mutation on Chromosome 5
DCC
Deleted in Colon Cancer
- Deleted on Chromosome 18
Likelihood of a parent passing DM 1 to child
2%-3%
Likelihood of a sibling of a person with DM 1 having it
7%
likelihood of developing DM 1 with a positive father
6% by age 20
Likelihood of developing DM 1 with a positive mother
1% by age 20
Is type 1 Diabetes 100% concordant in identical twins
No
What are the two hits of intervention in type 1 Diabetes?
1st hit infection
2nd hit selection of the self-reactive T cells
Major antigens increasing the risk of Diabetes 1
DR3 and DR4. Expressed in 95% of white parents with DM 1 and only 50% of the general population
What percentage of offspring of DM 2 parents will develop it compared to the general population
38% of the offspring of DM2 and 11% of general pop
Concordance of DM2 in MZ twins after age 50
> 90%
Pima Indians in AZ
50% have DM2 and Calpain 10 is the susceptibility gene which has been identified
Obesity BMI level
> 30 kg/ M^2
Genes linked to obesity
Leptin
Neuropeptide Y
Melanacortin-4 receptor
PS1 Gene
Contributing gene to familial Alzheimer’s. Located on chromosome 14. Disrupts Ca++ regulation in the mitochondria. Causing an increase in apoptosis
PS2 gene
Contributes to familial Alzheimer’s. Located on chromosome 1. 80% homology to the PS1 gene.
APP
Amyloid-beta Precursor Protein. Pt’s with Alzheimer’s show an increase in mRNA which codes for APP causing an increase in neuritic plaque.
APOE
Apolipoprotein E which is located on Chromosome 19. Show a large increase of the likelihood of developing Alzheimer’s Disease
Concordance rate for alcoholism in MZ twins
> 60%
Structural abnormalities of pt’s with schizophrenia
- Loss of grey matter
- Ventricular enlargement
- Decreased volume
Likelihood of offspring developing Schizophrenia with affected parents
13% if one parent is affected and 48% if both parents are affected
Susceptibility genes for schizophrenia
- DTNBP1 on chromosome 6 it produces a protein called dysbinden
- NRG1 on chromosome 8 produces neuroregulin which makes neurotransmitter receptors
Concordance rates for twins with schizophrenia
MZ 48%
DZ 17%
likelihood of parents passing bipolar onto children
50%
First degree relatives of a bipolar person are how many times more likely to develop it
7 times more likely
Gene associated with Bipolar disorder
Dopamine D4 receptor gene on chromosome 11
