Quiz 1 Flashcards
Phenotype
the observable train or set of traits that is created from your genetic makeup Ex: hair color, eye color, flower color, wrinkled seeds.
Genotype
an individual’s collection of genes, or can reference to two particular alleles that codes for a gene (AA, Aa, aa). Determines phenotype
Penetrance
the percentage of expression of a particular gene or set of genes. May be complete or incomplete.
4 base pairs of DNA
Adenine, Thymine, Cytosine, Guanine
Transcription
is the first step of gene expression, in which a particular segment of DNA is copied into RNA (mRNA) by the enzyme RNA polymerase. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language.
DNA transcribed into mRNA.
Translation
(mRNA)—produced by transcription from DNA—is decoded by a ribosome to produce a specific amino acid chain, or polypeptide. The polypeptide later folds into an active protein and performs its functions in the cell.
Chromosomal Structure
DNA is tightly wound around a histone to form nucleosomes that equal about 140 base pairs. Nucleosomes are linked to form chromatin that is further condensed into chromatin. 22 pairs and 1 pair of sex chromosomes.
Homozygous
both alleles are identical the individual is homozygous
Heterozygous
each allele is different
Allele
homologous copies of a gene…Human have two sets of each gene, once copy on each chromosome.
Locus
location of a particular gene on a chromosome
Germinal mutation
occurs during formation off an egg or sperm
somatic mutation
mutation occurs after conception
Chromosomal aberration
alteration in the number or the physical structure of a chromosome. Most pregnancies with these mutations end in spontaneous abortion.
Monosomy
only one chromosome of a pair is present
ex: Turner’s Syndrome
Trisomy
three chromosomes are present
Ex: Down’s Syndrome
Polysomy
one chromosome is present 4 or more times.
Causes of abnormal numbers of proteins
nondisjunction
Changes in phenotype
caused by deletions and insertions of a chromosomal region
Chromosomal abnormality associated with Down’s Syndrome
trisomy 21 - most common trisomy
3 physical features of a Down Syndrome child.
- decreased muscle tone.
- flat facial features
large, protruding tongue. - small nose
- Upward slant of eyes
- Abnormally shaped ears.
- Deep palmar crease
- hyperflexibility
- extra space between 1st and 2nd toes.
What are 3 medical complications associated with Downs Syndrome
- Cardiac defects
- intestinal malformations
- vision abnormalities
- hearing loss
- recurrent respiratory infections
- memory loss
- increased risk of Alzheimer’s at an early age.
Genotype of Kleinfelter
XXY
Effect of Kleinfelter Syndrome
usually sterile due to impaired spermatogenesis.
50% will develop breasts
3 Physical effects of Kleinfelter syndrome
- Frontal Baldness absent.
- Less chest hair
- Breast development
- Female type pubic hair pattern.
- small testicular size
- long arms and legs
- wide hips
- narrow shoulders
- Poor beard growth
Consequences of Kleinfelter syndrome
- small testes
- low sperm count
- elevated FSH and LH
- Decreased serum testosterone
- Abnormal arm and leg length due to testosterone deficiency
- increased risk of breast cancer and pulmonary disease.
- impaired psychosocial skills, including ADHD, impaired judgment and insight.
- impaired higher language skills.
- increased risk of Non Hodgkin’s Lymphoma, leg ulcers, diabetes, lupus
Turner Syndrome Genotype
XO
Physical features of Turner Syndrome
short stature Low posterior hairline heart shaped face short, wide chest prominent neck folds broad, wide chest with widely spaced nipples Coarctation of the aorta cubital valgus usually sterile, low estrogen small breasts
Consequences of Turner Syndrome
hearing loss hypothyroidism autoimmune thyroiditis elevated liver enzymes Primary Amenorrhea osteoporosis renal structure abnormalities diabetes Hypertension aortic dissection
what base pairs pair together
Adenosine-Thymine
Cytosine-Guanine
which chromosome abnormality on lecture 1 can increase the risk of Alzheimer’s disease at an early age
1, 14, 19, 21
In autosomal recessive patterns, what chance does each child have of inheriting an abnormal phenotype?
25%
In autosomal dominant patterns, what chance does each child have of inheriting an abnormal phenotype?
50%
What inheritance pattern occurs frequently in consanguinity?
Autosomal Recessive
What 2 inheritance patterns tend to skip generations?
Autosomal recessive
X-linked recessive
Which type of trait is passed from mother to all her offspring?
Mitochondiral inheritance
What needs to be restricted in the diet of a patient with PKU
Phenylalenine
Name the 3 germ layers that develop from the inner cell mass during the embryonic stage of development
Ectoderm, mesoderm, endoderm
What is the critical period for teratogenesis?
3-16 weeks due to impairment of organogenesis.
What is the medical category of a medication is the worst and has shown demonstrated fetal abnormalities as a result of medication?
Category X
- Name two of the three limb abnormalities that were associated with use of thalidomide
Ameilia - no limbs
Miromelia - partial abscence of a limb
Phocomelia - absence of long bones with hands and feet attached to trunk with small rudimentary bones
Name the two malignancies associated with DES daughters
Cervical cancer and vaginal cancer
This acne medication is one of the most potent teratogenic medications in use today
Isotrentinoin (accutane)
Which hypertension medication category is known to be teratogenic?
ACE inhibitors - the “prils”
Lisinopril, Ramipril Enalapril, Captopril
- Which medication can cause nasal hypoplasia and limb hypoplasia?
Warfarin (Coumadin)
“Floppy infant syndrome” can occur with which type of anti-anxiety medication?
Benzodiazepines
Describe three physical abnormalities associated with fetal alcohol syndrome?
- small head
- epicanthal folds
- flat midface
- smooth filthrum
- underdeveloped jaw
- thin upper lip
- short nose
- small eye openings
- low nasal bridge
- “railroad track ears”
- Ptosis - drooping eyelids
- decreased elbow pronation and supination
- incomplete extension of digits
- “hockey stick crease” defects in palmar crease
Vasoconstriction and hypertension mediate the effects of which illicit drug used in pregnancy?
Cocaine
Name 3 maternal effects from cocaine
Likely to be related to vasoconstriction and hypertension:
- MI
- Arrhythmias
- Aortic rupture
- CVA (stroke)
- Seizure
- Bowel Ischemia
- sudden death
Name three fetal effects from exposure to cocaine prenatally.
- spontaneous abortion
- fetal demise
- placental abruption
- Premature birth
- IUGR - intrauterine growth restriction
What does the TORCH acronym stand for?
T -Toxoplasmosis O - other infections R - Rubella C - Cytomegalovirus H - Herpes
Name two sources of toxoplasmosis.
Contaminated soil
Cat feces
undercooked meat
unfiltered water
Exposure to this agent can cause chorioretinitis, hydrocephalus and intracranial calcifications.
Toxoplasmosis
In what exposure do infants present with a white to bloody nasal discharge?
Syphilis
What virus presents with “mono-like” symptoms?
Cytomegalovirus
What virus in newborns presents with skin, eye and mouth manifestations and can spread to the CNS?
Herpes
Name the two hallmark changes that occur with Alzheimer’s Disease?
Amyloid Plaques and neurofibrillary tangles
Amyloid plaques
abnormal deposits of a protein called beta amyloid that is found in the space between neurons
Neurofibrillary Tangles
formed by clumps of tau protein, which is part of the structure of the microtubules that support the structure of the neuron
Describe three manifestations of Alzheimer’s Disease.
Memory deficits - especially facts and recall of recent events early in AD
Language changes - verbal disfluency, anomia, reduced vocabulary, diminished comprehension, circumlocution
Visuospatial skills - misplacement of items worsening navigation
reduced insight to own deficits
Apraxia or dyspraxia
loss of executive function
mild depression
Changes in olefactory function
Loss of sleep or fragmented sleep
How is early-onset AD inherited?
Autosomal Dominant in most cases
Name two of the three genes associated with early-onset AD?
Amyloid precursor protein (APP) Presenilin 1 (PSN1) Presenilin 2 (PSN2)
Which gene is most strongly linked with Late-onset AD?
APO epsilon 4 - increases risk by 3-8 fold depending on whether a person has 1 or 2 copies of the allele. 35-50% of people w/ AD have at least 1 copy of APOE epsilon 4
How is Huntington’s Disease inherited?
Autosomal Dominant pattern, only one copy is needed
Name three manifestations of Huntington’s Disease?
- Chorea
- Gait abnormalities
- Abnormal, slow eye movements, absence of smooth movements
- Psychiatric abnormalities: irritability, anxiety, depression, disrupted social relationships, paranoia, aggression, delusions
- Loss of insight, inflexibility, memory loss, impaired judgement
- Weight loss/ cachexia
How may CAG repeats are considered positive for Huntington’s Disease?
over 40 repeats (so 41 repeats for a diagnosis). The more CAG repeats, the earlier onset and increased severity of the disease. If inherited from your father, onset will occur 3 years earlier than if you had inherited HD from your mother.
How is CF inherited?
Autosomal recessive
What ion transport is affected in CF?
Chloride
Name three clinical manifestations in CF.
- Failure to thrive/ impaired growth - due to malabsorption of pancreatic insufficiency
- Chronic pulmonary infections
- Nasal Polyps, epistaxis, siusitis
- Chronic cough w/ or w/o sputum, hemoptysis
- Abnormal lung parynchema
- Cor Pulmonale R sided heart failure)
- Pancreatic inflammation and pancreatitis
- Steatorrhea - increased fat in stool
- CF is related to Diabetes Mellitus
- Liver damage, portal hypertension
- CF Males - 98% are infertile due to absence of Vas Defrens
Which gene is involved in NF1?
Neurofibromatosis 1 on chromosome 17
Name three clinical dermatologic manifestations of NF1.
- Cafe au Lat macules - 6 or more are indicatie of NF1
- Freckling, especially in areas of opposition such as axillary and inguinal regions
- Lisch nodules, small hamartomas of the iris, most common in adult NF1.
- Neurofibromas - plexiform or nodule
- Plexiform neurofibromas - may have hypertrichosis and cause severe disfigurement
What tumor of the eye occurs in 15% of NF1 patients?
Optic Gliomas
Name two bony manifestations of NF1.
- Pseudoarthrosis of the long bones.
- Bowing of legs
- Scoliosis
- Short Stature
- Osteoporosis
NF2 primarily causes tumors on what area of the body?
CNS and auditory nerves. Can have ocular manifestations as well
How is PKD usually transmitted?
Autosomal Dominant
PKD causes faster progression to what disease?
End Stage Renal Failure
Name three manifestations of PKD.
- Renal Lithiasis
- Hematuria
- Proteinuria
- Flank Pain
- Urinary Tract /Kindney infection
- Hypertension resulting from disturbances of renal perfusion
What lab calculation should you make before giving a patient with PKD medication?
Creatinin clearance
What is the most dangerous complication for a patient with PKD?
Intracranial Aneurysm occurs in about 10-20% of people w/ PKD
How is hereditary hemochromatosis inherited?
Autosomal Recessive
Over what age do patients with HHC usually present?
over 40 - this is due to the excess absorption over a period of years
What lab tests might you see elevated in HHC?
- liver enzymes
- Serum Iron
- CBC - (high WBCs due to increased infections)
Name three clinical manifestations of HHC.
Reversible: 1. Cardiomyopathy 2. Arrythmia 3. Abdominal pain,increased liver enzymes, hepatomegaly 4. Skin hyperpigmentation 5. Infection Permanent: 1. Cirrhosis 2. Hepatocellular carcinoma 3. Hypogonadism 4. Diabetes Mellitus 5. Hypothyroidism 6. Arthritis
Name the two factors deficiencies in Hemophilia A and B.
Factor 8 and Factor 9
How is hemophilia transmitted?
X-linked recessive
Name three clinical manifestations of hemophilia.
- Intracranial hemorrhage
- abnormal bleeding with procedures
- excessive bruising - disproportionate to the injury.
- hematomas
- hemarthroses
- epistaxis
- bleeding from pharynx after coughing
- Melena - blood in stool
- hematuria
- Menorrhagia - in female carriers
- delayed post-traumatic blessing, oozing, hemorrhage out of proportion to the injury
Which type of VWF is the worst and why?
Type 3 b/c you have no VFW that is able to function properly
How is sickle cell anemia transmitted?
Autosomal Recessive
Name three clinical manifestations of sickle cell anemia.
Infants and Children: 1. failure to thrive 2. anemia 3. splenomegaly 4. multiple infections 5. swelling in extremities due to vaso-occlusion Adult: 1. chronic anemia 2. jaundice 3. cholelithiasis 4. Aplastic crisis - cessation of RBC rpoduction caused by Strep infection, Epstein-Barr virus, Parvovirus B19, and certain meds. 5. tissue ischemia 6. sever abd pain 7. stroke 8. acute chest syndrome - chest pain, dyspnea, fever. 9. Renal necrosis 10. leg ulcers 11. priaprism 12. vision loss due to infarction
Name two dermatologic manifestations of familial hyperlipidemia.
Tendon Xanthomas
Xanthelasma
How is Marfan Syndrome inherited?
Autosomal Dominant or de-novo
What structure or tissue is basically abnormal in Marfan Syndrome?
Fibrillin = connective tissue is overly elastic
What structural abnormality with Marfan Syndrome is the major cause or morbidity and mortality?
Aortic Root Disease
What does dolichostenomelia and arachnodactyly mean?
Dolichostenomelia - arm span greater than body height
Arachnodactyly - spider like fingers
Name two tests/ maneuvers that indicate possible Marfan Syndrome.
Positive thumb sign
Positive wrist sign
Differentiate between pectus carinatum and pectus excavatum?
Pectus Excavatum- “funnel chest”
Pectus Carinatum- “pigeon chest”
Name three other clinical manifestations of Marfan Syndrome.
Hindfoot valgus - “L shape” “too many toes” sign
Pes Planus”
Name one way that hemophilia may present in a newborn.
excessive bleeding post-circumcision, bruising or hematoma after use of forceps or vacuum during delivery.
Christmas Disease
Factor 9 deficiency Hemophilia B
Classic hemophilia
Factor 8 deficiency
Name three clinical presentations of aortic dissection.
- Chest pain
- Upper back and L shoulder pain
- Hypotension (shock if severe)
- May have EKG changes (not always)
Name the four “Ps” in aortic aneurysm.
- Pallor
- Pulselessness
- Parasthesias
- Paralysis
Name one possible way to differentiate between familial and sporadic thoracic aortic aneurysms (TAA)
Familial TAA present at an earlier age than Sporadic TAA (56 vs. 64)
Familial TAAs involve the Ascending Aorta in 80% of cases
Name the four types of cardiomyopathies.
- Dialated - dilatation of at least one of the ventricles of the heart which results in impaired contraction of one or both ventricles
- hypertrophic - myocardium becomes thickened especially the L ventricle
- Restrictive - stiffening and rigidity of the ventricles due to replacement of normal myocardium by scar tissue, no hypertrophy of the ventricle
- Arrythmogenic - right ventricular myocardium replaced with scar tissue
Which two types of cardiomyopathies are most common.
Hypertrophic and Arrythmogenic
Name three manifestations of hypertrophic cardiomyopathy.
- Left ventricular hypertrophy
- Impaired left ventricular contractility
- Dyspnea on exertion
- Palpitations
- Chest pain
- Syncope
What is the lifetime risk for breast cancer?
10-13% or a 1/10-1/7
What percentage of breast cancers are attributable to genetics?
5-10%
What group in the U.S. are at a significant risk of developing hereditary breast cancer?
Ashkenazi Jews
How are BRCA genes inherited?
Autosomal Dominant
What are the normal functions of normal BRCA1 and BRCA2 genes?
Tumor Suppressors
preserve the structure and function of chromatids and chromosomes
repair breaks in DNA
Which mutation is associated with a higher risk of breast cancer between the two?
BRCA 1
Name two other cancers types that may be increased in BRCA1 mutation carriers.
fallopian tube primary paritoneum pancreas esophageal stomach prostate
What is the lifetime risk of ovarian cancer?
lifetime risk is greater than 1%
40% in BRCA1
18% in BRCA 2
At what age do you start annual mammograms in patient with HBOC?
25-35 years old
Name two factors that influence the development of colorectal cancer in the general population.
Physical inactivity poor diet tobaccos use obesity lower rates of colorectal sreening
In an older person, what may be the first presenting sign of colorectal cancer and warrants investigation?
Anemia of unexplained origin
Name two things that differentiate FAP from attenuated FAP.
- Number of polyps - FAP: hundreds to thousands may develop. attenuated FAP - fewer polyps (
In Lynch Syndrome, what two things are different and frightening about the polyps?
Polyps are flatter, larger, and have a rapid transformation into CA.
Name two other associated malignancies for Lynch Syndrome patients.
- Uterine cancer
- Ovarian cancer
- Gastric cancer
- Small bowel cancer
- Biliary tract cancer
- Upper urinary tract cancer
- Pancreatic cancer
- Skin cancer
- Brain cancer
Name the syndrome associated with colorectal cancer that causes macules on the lips and oral regions.
Peutz-Jehgers Syndrome
What food is best associated with the city associated with the chromosomal abnormality of chronic myelogenous leukemia?
Philly Cheese Steak
Philadelphia Chromosome
What three blood cells proliferate in CML?
The “Phils”
Eosiniphil
Basophil
Neutrophil
Name three manifestations of CML.
increased:
infection
anemia
bleeding
What does ABCD stand for in malignant melanoma?
A - Asymmetrical
B - borders
C - color
D - diameter
Which type of melanin produces higher risk individuals for malignant melanoma?
Pheomelanin
Two types of Melanin
Eumelanin
Pheomelanin
