3. Genetics Flashcards
(103 cards)
1
Q
Can a disorder be congential but not hereditary?
A
Yes! congenital simply means “born with”- hereditary is familial
2
Q
what disease is associated with chromosome 15?
A
Imprinting Dx’s: prader Willi and Angelmann
3
Q
what disease is associated with chromosome 16?
A
APCKD
4
Q
what disease is associated with chromosome 5?
A
Familial Adenomatous Polyposis (APC gene)
5
Q
what disease is associated with chromosome 4?
A
Hungtington
6
Q
what disease is associated with chromosome 17?
A
NF1
7
Q
what diseases are associated with chromosome 22?
A
NF2, DiGeorge/Velocardiofacial syndromes
8
Q
what disease is associated with chromosome 3?
A
VHL (Von Hippa Lindau)
9
Q
what disease is associated with chromosome 7?
A
Cystic Fibrosis (CFTR gene)
10
Q
what disease is associated with chromosome 21?
A
Down’s Syndrome
11
Q
what disease is associated with chromosome 18?
A
Edwards
12
Q
what disease is associated with chromosome 13?
A
Pataus
13
Q
what type of disorders are associated with chromosomes 13,14,15,21,22?
A
Robertsonian translocations
14
Q
what disease is associated with chromosome 5?
A
Cri du Chat
15
Q
what disease is associated with chromosome 7?
A
Williams
16
Q
what disease is associated with chromosome 13?
A
Rb
17
Q
Give an example of codominance.
A
Blood group types
18
Q
With what type of inheritance is variable expression and incomplete penetrance associated with? Give an example of each.
A
Autosomal Dominant; NF1 and mit. diseases (variable expression), ?
19
Q
What is Pleiotropy? What is the opposite of Pleiotropy? Give an example of each.
A
1 gene has greater than 1 phenotypic effect; locus heterogeneity (many different mutations can cause the same phenotype); PKU; albinism, deafness, Marfanoid habitus (Marfans, MEN 2B, homocystinuria)
20
Q
what 3 genetic disorders can cause Marfanoid habitus?
A
marfans, homocystinuria, MEN 2B
21
Q
What is imprinting disease? Give 2 examples
A
When the disease manifestation depends on from who the gene deletion was inherited from d/t methylation that occurs; Prader Willi and AngelMann
22
Q
What type of diseases exhibit anticipation?
A
Trinucleotide expansion diseases
23
Q
What is loss of heterozygosity? name an example.
A
When the 2nd hit of the allele is what causes the disease; sporadic retinoblastoma
24
Q
T/F Loss of heterozygosity is the rule with oncogenes.
A
False! This is the rule for tumor suppressor genes (p53, Rb, BAX)
25
T/F Sporadic Retinoblastoma results in unilateral ocular tumor in children with osteosarcomas.
False- first part of question is right- sporadic is unilateral, but only familial is associated with osteosarcomas (Rb mutation is in all cells!)
26
Name two reasons why mosaicism might occur.
lyonization; nondisjunction in mitotic divisions during embryonic period
27
What is heteroplasmy?
presence of normal and mutated mtDNA (like mosaicism except in mit)
28
what is uniparental disomy? give an example of a disease it can cause.
when child gets two chromosomes from one parent; imprinting dx
29
T/F in all recessive diseases, prevalence of disease =q^2
false! in x linked, in males, prevalence is = q
30
With what tool are Prader Willi and Angelman diagnosed?
FISH
31
what is imprinting?
when one allele on a gene is only expressed and the other is methylated/inactivated; during gametogenesis one of the alleles is methylated because the gamete from the other sex will provide those characteristics for the child
32
what disease manifestations result in Prader Willi syndrome? is the deletion a result from the father or mothers chromosome?
mental retardation, obesity, short stature, hypogonadism, hypotonia, hyperphagia; father
33
what disease manifestations result in AngelMan syndrome? is the deletion a result from the father or mothers chromosome?
mental retardation, excessive laughter, seizures, ataxia, "happy puppet"
34
What type of proteins have AD mode of inheritance?
structural (constitutively active)
35
T/F AD disease present early
false! usually present late
36
T/F AD diseases are usually pleiotropic
True!
37
T/F AR disease are usually enzymatic
True!
38
T/F AR disease is usually not very severe, or less so than AD at lease
False! opposite
39
T/F heterozygous females in X linked recessive disease are not affected
false! can be d/t lyonization
40
T/F daughters of Xlinked recessive diseased fathers are all carriers
TRUE
41
T/F daughters of Xlinked dominant diseased fathers are all carriers
false- all are diseased!
42
What are two examples of X linked Autosomal Dominant disease?
hypophosphatemia rickets and Alports
43
What is hypophosphatemia rickets? Can it be treated with Vit D?
In ability to reabsorb phosphate from renal tubular cells results in osteomalacia due to defective bone mineralization; no
44
T/F All offspring of affected males with a mit disease can show disease.
False- none!
45
what is the function of mitDNA?
encode enzymes for oxphos mit reactions
46
Why do mitochondrial diseases exhibit variable expression?
heteroplasmy
47
What are ragged red fibers?
collections of abnormal mit collecting under sarcolemmal membranes and results in distortion of myofibrils
48
Other than ragged red fibers and lactic acidosis, what else is common in mit myopathies?
neurologic lesions and cardiomyopathies (ox phos!)
49
What is the inheritance of myoclonic epilepsy?
mitochondrial inheritance
50
What is lebers hereditary optic neuropathy? what is the main clinical symptom? and what is its mode of inheritance?
degeneration of retinal ganglion cells and axons; acute loss of central vision; mit. inheritance
51
what is achondroplasia? what type of inheritance?
cell signaling defect in FGF receptor resulting in dwarfism and short limbs with normal head and trunk; AD
52
T/F achondroplasia is associated with advanced maternal age
False- paternal
53
T/F APCKD can be unilateral.
FALSE
54
What else becomes cystic often in APCKD? other than cystic presentations what else do APCKD patients present with?
liver; berry aneurysms (d/t hypertension!), and mitral valve prolapse
55
what inheritance pattern is Type IIA hypercholesterolemia? do heterozygotes present with disease? do homozygotes present?
AD: yes! most common presentation; very rare (700 mg/dl cholesterol level!)
56
what is the inheritance pattern of hereditary hemorrhagic telangiectasia or Olser Weber Rendu Syndrome? What is it?
AD; disorder of blood vessels that results in telangietasias, skin discolorations, and AVMs (arteriovenous malformations)
57
what is a telangiectasia? where can they be found?and what is a common result of them?
dilated capillaries and veins; skin, mucous membranes, GI, resp, urinary tracts; rupture and can cause epistaxis, hemorrhage, GI bleeding
58
What is the inheritance pattern of hereditary spherocytosis?
AD
59
what is the pathogenesis of Huntingtons disease?
gain of function gene after expansion results in overproduction of huntingtin protein that in overproduction results in toxicity to neurons in the caudate--\> caudate atrophy and decreased levels of GABA and Ach
60
what are the clinical symptoms of Huntingtons disease? when does it present?
depression, progressive dementia, choreiform movements; between the ages of 20 and 50
61
What is the mode of inheritance of Marfans?
AD
62
what is the mode of inheritance of Huntingtons?
AD (trinucleotide expansion is not a mode of inheritance)
63
what are the clinical symptoms of Marfans?
HEART, SKELETON, and EYES: arachnodactyly, long limbs, cystic medial necrosis of aorta resulting in aneurysms (and eventual dissection), floppy mitral valve (prolapse and regurg!), subluxation of lens
64
what is the mode of inheritance for the multiple endocrine neoplasias?
AD
65
With what gene are MEN 2A and 2B associated with?
ret
66
What are the clinical symptoms of NF1?
cafe au lait spots, optic pathway gliomas, lisch nodules, scoliosis, neural tumors
67
what are lisch nodules?
pigmented iris hamartomas
68
what are the clinical symptoms of NF2?
bilateral acoustic schwannomas, juvenile cataracts
69
T/F the mode of inheritance for both NF disease is AR
false! Both AD!
70
what is the inheritance of Tuberous Sclerosis?
AD
71
What is the inheritance of Von Hippel Lindau disease?
AD
72
what is the inheritance of CF? what is the pathogenesis of the disease?
AR; trinucleotide deletion results in loss of a Phe aa on CFTR gene on chrom 7- the result is a mutated CFTR channel that gets degraded in the ER before reaching the surface; the purpose of CFTR is to increase Cl secretion in luminal secretions and reabsorb Cl from sweat secretion
73
T/F CFTR channel secretes Cl into sweat
False! reabsorbs Cl; secretes NaCl in luminal secretions
74
What luminal secretions are affected in CF? What is wrong with the secretions?
respiratory, seminal fluid, pancreatic, gallbladder; very thick without NaCl to pull water
75
What are the resp. clinical symptoms of CF?
thick mucus plugs lungs recurrent pulmonary infections (pseudomonas and aureus), chronic bronchitis, bronchiectasis (which can lead to cor pulmonale!); biofilms form on resp tract
76
what are the GI clinical symptoms of CF?
chronic pancreatitis leads to type 1 diabetes, pancreatic insufficiency leads to ADEK deficiencies, malabsorption and steatorrhea, blocked gallbladder ducts leads to secondary biliary cirrhosis
77
what systems are affected by CF?
pulmonary, GI, reproductive (infertility in male due to absence of vas deferens and seminal fluid thickness)
78
what are two clinical symptoms of newborns with CF? and whats a lab value of a newborn with CF?
meconium ileus and failure to thrive; negative serum immunoreactive trypsin
79
how is CF diagnosed?
increased concentration of Cl ions in sweat test
80
How is CF treated? how does it work?
Nacetyl cysteine; breaks disulfide bridges of mucus plugs
81
what is the mode of inheritance of the muscular dystrophies? what is the pathogenesis of the disease?
X linked recessive; deletion of the dystrophin gene (connects actin to the membrane glycoprotein) due to frame shift mutation- lack of dystrophin results in muscle breakdown which gets replaced by fibrofatty tissue and collagen
82
what are the clinical symptoms of duchennes muscular dystrophy?
starts before age 5 with with pelvic girdle weakness with use of Gowers maneuver to stand up, it then progresses superiorly with muscle weakness (type 1 and 2!); waddling duck gait; hyporeflexia; pseudohypertrophy of calf muscles d/t fibrofatty replacement; cardiac myopathy
83
how is muscular dystrophies diagnosed?
increased CPK and muscle biopsy
84
what is the difference b/w beckers and duchennes muscular dystrophy?
beckers is less severe (instead of deletion is either defect or deficiency) with later presentation
85
what is the pathogenesis of fragile x syndrome?
a trinucleotide repeat disorder results in faulty methylation and thus expression of the FMR1 gene on the X chromosome (x linked recessive mode of inheritance)
86
what are the clinical symptoms associated with fragile X syndrome?
macroorchitism, big ears, big jaw, mental retardation (2nd mcc!), mitral valve prolapse, long face
87
What are the four trinucleotide expansion disease and what are the expansions?
Myotonic Dystrophy (CTG), Huntington (CAG) Friedricks Ataxia (GAA), Fragile (CGG)
88
what are the three mc autosomal trisomies in decreasing order?
Downs (21), Edwards (18), Pataus (13); also in increasing severity
89
what is the mcc of an autosomal trisomy?
meiotic nondisjunction in mothers gametes during the first meiosis
90
what are the clinical symptoms of Down syndrome?
mental retardation, flat faces, simean crease, epicanthal folds, ASD, duodenal atresia causing Hirshsprungs disease, redundant skin at the nape of neck, slanted palpebral fissures, hypotonia
91
what is there on increased risk of with Downs?
ALL and Alzheimers
92
what is the mc chromosomal disorder?
Downs
93
what are the results of the pregnancy screen for Downs?
decrease AFP, increased BCHG, decreased estriol, increased inhibin A
94
What does ultrasound show in Downs?
increased nuchal translucency
95
what is the confirmation of Downs?
amniocentesis karyotyping
96
what are the clinical findings in edwards syndrome?
mental retardation, rocker bottom feet, micrognathia (small jaw), low set ears, clenched hands with polydactyly, congenital heart disease
97
what are the clinical findings in patau syndrome?
mental retardation, rocker bottom feet, micropthalmia, microcephaly, cleft lip/palate, holoprosoncephaly, polydactyly
98
what is a robertsonian translocation? what does it mean if its balanced?
its when two acrocentric chromosomes combine their long arms (and short arms disappear); when the translocation is functional
99
what is a common result of unbalanced robertsonian translocation?
chromosomal imbalance (downs for ex)
100
what are the symptoms of cri du chat syndrome? what is the pathogenesis?
microcephaly, mental retardation, high pitched mewing/crying, epicanthal folds, cardiac abnormalities; microdeletion on short arm of chrom 5
101
what are the symptoms of williams syndrome? what is the pathogenesis?
distinctive elfin faces, mental retardation, hypercalcemia d/t sensitivity to vit D, well developed verbal skills and extreme friendliness, CV problems
102
What are the two 22q11 deletion syndromes? what is their pathogenesis? what is the difference between them?
DiGeorge and Velocardiofacial; deletion on chromosome 22q11 results in aberrant dev of 3rd and 4th branchial pouches; digeorge has thymic and parathyroid prob, velocardiofacial has palate and facial instead
103
what are the general symptoms of 22q11 chromosomal deletion? why is it that these occur?
Cleft palate, Abnormal faces, thymic aplasia (t cell def), Cardiac defects, hypocalcemia (secondary to hypoparathyroid); 3rd and 4th branchial pouch aberrant development
