Term
| What is the most common form of DNA variation? |
|
Definition
| single nucleotide polymorphism |
|
|
Term
|
Definition
| loss or gain of entire chromosomes |
|
|
Term
|
Definition
| rearrangement of genetic material with visible structural changes in the chromosomes |
|
|
Term
trinucleotide repeat mutations
What are the most commonly involved? |
|
Definition
amplification of a 3 nucleotide sequence
cytosine and guanine |
|
|
Term
| fragile x syndrome is an example of what type of mutation? What are the repeats/how many? What gene does this effect? |
|
Definition
trinucleotide repeat mutation
250-4000 of CGG
prevents normal expression of FMR-1 gene |
|
|
Term
| What are the factors involved in multifactorial inheritance? |
|
Definition
| both genetic and environmental |
|
|
Term
|
Definition
| a single gene mutation may result in many different effects |
|
|
Term
|
Definition
| mutations at several different loci can produce the same trait |
|
|
Term
| When is the age of onset for an autosomal dominant disorder? |
|
Definition
| age of onset is usually delayed |
|
|
Term
| reduced penetrance vs variable expressivity |
|
Definition
1. some people have the mutant gene but do not express it
2. disease is expressed differently in different people |
|
|
Term
| familial hypercholesterolemia |
|
Definition
| 50% loss of LDL receptors leads to elevation in cholesterol and predisposes to atherosclerosis |
|
|
Term
| Dominant negative, and example of one |
|
Definition
a mutant allele impairs the function of a normal allele
collagen helix requires 3 normal chains-if any chains are mutant, collagen cannot form |
|
|
Term
| example of gain of function mutations |
|
Definition
| increase in erythropoeitin receptors |
|
|
Term
| complete penetrance is common in what type of inheritance? |
|
Definition
|
|
Term
| In what type of inheritance is onset usually early? |
|
Definition
|
|
Term
| do females express x-linked recessive disorders? |
|
Definition
| they do partially most of the time due to random x inactivation |
|
|
Term
| what is the basis for albinism |
|
Definition
| lack of tyrosinase results in a melanin deficiency |
|
|
Term
| what gene is defect in mar fans? Where are microfibrils abundant? |
|
Definition
fibrillin-1
aorta, ligaments, ciliary zonules |
|
|
Term
| in mar fans, the ratio of the upper body to the lower body is..... |
|
Definition
|
|
Term
| what are some of the symptoms of mar fan's syndrome |
|
Definition
tall with long arms and legs
double jointed
kyphosis, scoliosis
pectus excavatum, pigeon breat deformity
octopi lentos (subluxation or dislocation of the lens)
cystic medionecrosis
aortic insufficiency
aortic dissection |
|
|
Term
| what is the most common cause of death for a mar fan's patient? |
|
Definition
| ruptured aortic dissection |
|
|
Term
| diagnosis of mar fans must have major involvement of 2 of the 4 and a minor involvement in another of which 4 systems? |
|
Definition
|
|
Term
| What protein is irregular in ehlers-danlos syndrome? what tissues are most effected? |
|
Definition
fibrillar collagen
skin,ligaments, and joints |
|
|
Term
| Is ehlers-danlos an example of clinical heterogeneity? |
|
Definition
| yes because there is a variety of defects with different patterns of inheritance |
|
|
Term
| collagen fibrils lack this in ehler's danlos |
|
Definition
|
|
Term
| Joint dislocation, hyper extensible skin, rupture of colon and large arteries, and corneal rupture is common for what disorder? |
|
Definition
|
|
Term
| kyphoscolios type of ehler's danlos has a mutation in which gene? what are the effects? |
|
Definition
lysyl hydroxyls
required for hydroxylation of lysine residues in collagen synthesis, normal cross-linking cannot occur (collagen lacks structural stability) |
|
|
Term
| vascular type of ethlos-danlos has a defect in which gene? what is the effect? |
|
Definition
various abnormalities of type 3 collagen
blood vessels and intestines are rich in type 3 collagen
spontaneous rupture can occur |
|
|
Term
| arthrochalasia and dermatosparaxis types of ethler's danlos has a defect in which gene? |
|
Definition
| defects in the conversion of type 1 pro collagen to collagen |
|
|
Term
| Classical type of ehlers danlos has a defect in which gene? |
|
Definition
| mutations in genes for type 5 collagen |
|
|
Term
| where is the mutation in familial hypercholesterolemia? |
|
Definition
| a mutation in the gene encoding the receptor for low density lipoprotein, which is involved in the transport and metabolism of cholesterol |
|
|
Term
| How common is familial hypercholesterolemia? what are the effects? what about homozygous individuals? |
|
Definition
tendinous xanthomas, premature atherosclerosis
very common (1/500)
homozygous has 5-6x normal cholesterol levels, resulting in skin xanthomas, early atherosclerosis where MI may develop before age 20
heterozygotes just have 2-3x the normal amount |
|
|
Term
| explain cholesterol metabolism |
|
Definition
vldl is secreted from liver
lipoprotein lipase cleaves VLDL to IDL
IDL has apoprotein B-100 and E
LDL receptor recognized half of the IDL particles and recyles back to VLDL
the other half is taken up by the liver, removing triglycerides and apoprotein E creating cholesterol-rich LDL |
|
|
Term
|
Definition
| coated pits (on liver and internalized by invagination to form coated vesicles) |
|
|
Term
| what happens to LDL particles after it enters the liver? |
|
Definition
| vesicle will fuse with lysozymes and receptors are recycled, cholesterol esters are broken down into free cholesterol |
|
|
Term
| what effects does free cholesterol have once it enters the cytoplasm? |
|
Definition
supresses cholesterol synthesis by inhibition of HMG CoA reductase
stores cholesterol
suppresses the synthesis of LDL receptors |
|
|
Term
| is familial hypercholesterolemia one mutation? |
|
Definition
| no over, 900 mutations have been found |
|
|
Term
| There is increased synthesis of LDL in FHC because |
|
Definition
| IDL uses LDL receptors for transport into the liver, so impaired IDL transport diverts more on the path to become LDL |
|
|
Term
| what is the major source of plasma LDL? |
|
Definition
| IDL that is converted to LDL (thoser IDL particles that are not taken up by LDL receptors in the liver) |
|
|
Term
| 5 groups of LDL recetpor mutations |
|
Definition
S-A-A-P-D
1:no synthesis
2: accumulate in ER (receptors)
3: abnormal binding
4: fail to localize in coated pits
5: fail to dissociate from the LDL, and not recycled |
|
|
Term
| What is the purpose of mannose-6-phosphate? |
|
Definition
| label put on in golgi that sends protein to lysosomes |
|
|
Term
| what organs are often affected by a lysosomal storage disorder? |
|
Definition
| spleen and liver because they are rich in mononuclear phagocytes |
|
|
Term
| what is the severe deficiency in tay-sachs disease? what accumulates? |
|
Definition
hexosaminidase A
GM2 gangliosides accumulate |
|
|
Term
| What proliferates in tay-sachs? |
|
Definition
|
|
Term
| cherry-red spot in macula is a clinical sign of? |
|
Definition
| tay-sachs, nieman-pick disease |
|
|
Term
| what is the pathogenesis of tay-sachs? |
|
Definition
normal at birth, signs start about 6 months of age
motor incoordination, dementia, blindness until a vegetative state sets in and death at 2-3 years of age |
|
|
Term
| what are the microscopic findings in tay-sachs? |
|
Definition
whorled, "onion-like" includsions in lysosomes
cytoplasmic, fat-filled vacuoles |
|
|
Term
| what is the deficiency in niemann-pick disease |
|
Definition
| sphingomyelinase deficiency with lysosomal accumulation of spinghomyelin |
|
|
Term
| what are the clinical findings in niemann-pick disease? |
|
Definition
MASSIVE SPLENOMEGALY
vomiting, fever, enlarged lymph nodes |
|
|
Term
| what is the difference between niemann-pick type A and type B |
|
Definition
type a is severe infantile form, with neurologic involvement and death by 3 years
type b is adult form with organomegaly but no neurologic impairment |
|
|
Term
| what are the microscopic findings in niemann pick disease? |
|
Definition
zebra bodies (parallel palisaded lemellae of lysosomes
foamy cytoplasm filled with small vacuoles
enlarged phagocytes because of lysosome distention with sphingomylein and cholesterol |
|
|
Term
| what is the most common lysosomal storage disorder? |
|
Definition
|
|
Term
| what enzyme is deficient in gaucher disease? |
|
Definition
| glucocerebrosidase, an enzyme that normally cleaves the glucose residue from ceramide |
|
|
Term
| what is characteristic of gaucher disease type 1 |
|
Definition
most common form (99%)
non-neuronopathic, only accumulate in phagocytic cells
mainly involves spleen and skeleton
NO BRAIN INVOLVEMENT |
|
|
Term
| what is characteristic of gaucher disease type 2? |
|
Definition
acute neuronopathic
infantile acute cerebral pattern with early death due to absolutely NO glucocerebrosidase activity |
|
|
Term
| what is characteristic of gaucher disease type 3? |
|
Definition
| intermediate between type 1 and 2; both systemic and cns problems but a later onset |
|
|
Term
| what are the microscopic findings in gaucher disease? |
|
Definition
gaucher cells
enlarged phagocytic cells with fibrillary cytoplasm that resembles CRUMPLED TISSUE PAPER
stains positive with PAS |
|
|
Term
| what is the enzyme deficiency with mucopolysaccharidoses? |
|
Definition
group of disorders with deficiencies in lysosomal enzymes that degrade mucopolysaccharides (GAGs)
chains accumulate in the lysosome |
|
|
Term
| mucopolysaccharidoses follows this mode of inheritance with one exception |
|
Definition
autosomal recessive
hunter syndrome is x-linked recessive |
|
|
Term
| what are the microscopic findings of mucopolysaccharidoses |
|
Definition
| balloon cells (enlarged cells distended by lysosomes filled with mucopolysaccharidoses) |
|
|
Term
| what are the clinical features of mucopolysaccharidoses? |
|
Definition
coarse facial features
clouding of cornea
joint stiffness
mental retardation
hepatosplenomegaly
valvular lesions
sub endothelial arterial deposits leading to myocardial ischemia |
|
|
Term
|
Definition
a type of mucopolysaccharidoses
one of the most severe forms
hepatosplenomegaly by 6-24 months
death by 6-10 years |
|
|
Term
|
Definition
a type of mucopolysaccharidoses
milder clinical course with the absence of corneal clouding, remember this is x-linked recessive |
|
|
Term
| how are glycogen molecules linked? |
|
Definition
| alpha-1,4 linkages of glucose |
|
|
Term
| what does acid maltase doe? |
|
Definition
| lysosomal degradation of glycogen |
|
|
Term
|
Definition
| deficiency of glucose-6-phosphatase |
|
|
Term
| what are some of the clinical manifestations of myopathic glycogenoses? |
|
Definition
| muscle cramps after exercise and failure of exercise-induced rise in blood lactate levels |
|
|
Term
|
Definition
| deficiency of muscle phophorylase |
|
|
Term
|
Definition
acid maltase deficiency, lysosomal storage of glycogen
cardiomegaly is most prominent |
|
|
Term
| alkaptonuria (ochronosis) is a autosomal ______ disorder with a lack of _______ that inhibits the ability of the body to metabolize _______ and causes an accumulation of _________ |
|
Definition
recessive
homogentisic oxidase
phenyalanine/tyrosine
homogentisic acid |
|
|
Term
| alkaptonura clinical manifestations include |
|
Definition
blue-black pigmentation in ears, nose cheek
pigment in joint cartilage that causes brittleness and arthritis in early childhood
urine turns black with oxidation |
|
|
Term
| Neurofibromatosis type 1 is an autosomal _____ disorder that causes a mutation in tumor suppressor gene _______. |
|
Definition
|
|
Term
| Multiple neurofibromas are characteristic of what and where do they attach? |
|
Definition
neurofibromatosis type 1
tumors attached to or within nerve trunks found on the skin or internally |
|
|
Term
| what are the microscopic findings in neurofibromatosis type 1? |
|
Definition
| proliferation of all schwann cells, axons, fibroblasts |
|
|
Term
| Cafe au alit spots are characteristic of what? |
|
Definition
neurofibromatosis type 1, 6 or more spots greater than 1.5 cm is highly suggestive
ALSO SEEN IN NF TYPE 2 |
|
|
Term
|
Definition
| pigmented hamartomas of the iris |
|
|
Term
| what are some of the clinical findings in neurofibromatosis type 1? |
|
Definition
tumors found in nerves, cutaneously
2-4x risk of developing other neoplasms
tendency for reduced intelligence |
|
|
Term
| characteristics of neurofibroatosis type 2 |
|
Definition
mutation of NF-2
much less common then type 1
BILATERAL ACOUSTIC SCHWANNOMAS
multiple meningiomas, gliomas
cafe au alit spots but not lisch nodules |
|
|
Term
| g banding is accomplished by which stain? |
|
Definition
|
|
Term
| disorders with multifactorial inheritance result from a combination of ______ factors and ____ or more mutant genes |
|
Definition
|
|
Term
|
Definition
| x chromosome, short arm, 2nd region, 1st band, 2nd sub-band |
|
|
Term
|
Definition
| whole chromosomes can be labeled, number of chromosomes analyzed at once is limited by number of probes that excite different wavelengths of light |
|
|
Term
| spectral keryotying (SKY) |
|
Definition
entire genome can be visualized at once
uses combination of 5 flurochromes and computer-generated signals |
|
|
Term
| spectral keryotying (SKY) |
|
Definition
entire genome can be visualized at once
uses combination of 5 flurochromes and computer-generated signals |
|
|
Term
| what is the definition of aneuploidy? |
|
Definition
| ANY number of chromosomes other than an exact multiple of haploid |
|
|
Term
| can a euploid cell contain 69 chromosomes? |
|
Definition
| yes (it is a multiple of haploid) |
|
|
Term
| what are the two ways nondisjunction can occur? |
|
Definition
failure to separate
anaphase lag |
|
|
Term
| what are the two types of chromosomal deletions? |
|
Definition
interstitial and terminal
interstitial has 2 breaks with loss of material and fusion of broken ends
terminal has a single break in a chromosome producing a fragment with no centromere |
|
|
Term
|
Definition
| one arm is lost and one is duplicated |
|
|
Term
| Does translocation cause any phenotypic changes? |
|
Definition
| no, but at risk of producing abnormal gametes |
|
|
Term
| robertsonian translocation |
|
Definition
| a translocation between 2 acrocentric chromosomes, break occurs close to the centromere |
|
|
Term
| Down syndrome is caused by trisomy _____ in 95% of the cases, andtranslocation or mosaicism in the rest. |
|
Definition
|
|
Term
| clinical manifestations of down syndrome |
|
Definition
flat facial profile
oblique palpebral fissures
epicanthic folds
mental retardation
congenital heart disase
atresia of esophagus or small bowel
10-20x risk of leukemia
thyroid autoimmune, lung infections
equivalent to alzheimer's by 40 |
|
|
Term
| trisomy 13 (patau syndrome) |
|
Definition
cardiac defects
mental retardation
polydactyly (extra fingers or toes)
cleft lip and palate
rocker-bottom feet
death within days to month of birth |
|
|
Term
| trisomy 18 (edwards syndrome) |
|
Definition
cardiac defects
mental retardation
overlapping figers
renal malformations
micrognathia (undersized jaw)
rocker-bottom feet
death within days to months of birth |
|
|
Term
| 22q11.2 deletion syndrome |
|
Definition
"Catch-22"
cardiac defects
abnormal facies
thymic and t cell abnormalities
cleft palate
hypocalcemia
deletion on chromosome 22 |
|
|
Term
|
Definition
a type of 22q11.2 deletion syndrome
thymic hypoplasia
parathyroid hypoplasia
cardiac malformations
mild facial anomalies |
|
|
Term
| velocardiofacial syndrome |
|
Definition
a type of 22q11.2 syndrome
facial dysmorphism
cleft palate
cv anomalies
learning disabilities |
|
|
Term
| which are better tolerated, sex or autosomal imbalances? |
|
Definition
| sex (inactivation of all but one x chromosome, limited genetic material on the y chromosome) |
|
|
Term
|
Definition
only one x chromosome is genetically active
random inactivation of either x occurs ealy in embryonic life |
|
|
Term
|
Definition
| a gene product (RNA) that coats inactive x to silence it |
|
|
Term
|
Definition
| dictates testicular development |
|
|
Term
|
Definition
| testes-specific genes involved in spermatogenesis |
|
|
Term
| with the higher number of sex chromosomes there is an increased risk for what? |
|
Definition
|
|
Term
| Male hypogonadism that occurs with two or more x and one or more y chromosomes |
|
Definition
|
|
Term
| what are the clinical manifestations of klinefelter? |
|
Definition
abnormally long legs
small atrophic testes
small penis
lack of secondary male characteritic
elevated FSH and estrogen levels
reduced levels of testosterone
reduced spermatogenesis |
|
|
Term
| what are the associated disorders with klinefelters? |
|
Definition
breast cancer
extragonadal germ cell tumors
autoimmune disease |
|
|
Term
|
Definition
| 45,x and normal or abnormal cell types |
|
|
Term
|
Definition
| swelling at the nape of the neck due to distended lymphatics |
|
|
Term
| clinical manifestations of turner syndrome |
|
Definition
cystic hygroma
congenital heart disease (coarctation of the aorta, bicuspid aortic valve
failure to develop secondary sexual characteristics
short stature
primary amenorrhea
autoantibodies to thyroid gland
webbed neck |
|
|
Term
| what is a true hermaphrodite? what is the karyotype? |
|
Definition
has both ovarian and testicular tissue (ovotestes)
46, xx or 46,XX/46, XY mosaics |
|
|
Term
| what is a pseudohermaphrodite |
|
Definition
| disagreement between the phenotypic and gonadal sex |
|
|
Term
| female pseudohermaphrodite |
|
Definition
xx with normal ovaries but with male external genitalia
caused by excessive exposure to androgenic steroids during early gestation
most often due to CONGENITAL ADRENAL HYPERPLASIA in the fetus |
|
|
Term
|
Definition
testicular tissue is present, but with female genitalia
xy with testes
most common form is TESTICULAR FEMINIZATION due to mutations in the gene for the androgen receptor |
|
|
Term
| fragile x syndrome is a type of _________ disorder involving a mutation of ______ gene on the ______arm of the _____chromosome |
|
Definition
triplet repeat disorder
fmr-1
long
x |
|
|
Term
normal repeats for fragile x syndrome
permutation
full mutation |
|
Definition
10-55 CGG
55-200 CGG
200-4000 CGG |
|
|
Term
| which carrier is worse for fragile x, the male or female? |
|
Definition
| female because it often passes on a dramatic amplification of the repeats |
|
|
Term
| clinical manifestations of fragile x syndrome |
|
Definition
low iq
long face with large mandible
large everted ears
macroorchidism
hyper extensible joints
high arched palate
mitral valve prolapse |
|
|
Term
|
Definition
| inheritance of both chromosomes of a pair from the same parent |
|
|
Term
|
Definition
| deletion of paternal chromosome 15 band q12 (normally only the paternal allele of a specific gene is functional) |
|
|
Term
| clinical manifestations of prader-willi |
|
Definition
short staturehypotonia
obesity
small hands and feet
hypogonadism |
|
|
Term
|
Definition
deletion of maternal chromosome 15 band q12
normally only the maternal allele of a specific gene is functional |
|
|
Term
| clinical manifestations of angel man syndrome |
|
Definition
mental retardation
ataxic gait
seizures
inappropriate laughter "happy puppets" |
|
|
