Genetics

Front 1

Prader Willi Syndrome:
Phenotype
Interitance pattern
genetic characteristics

Back 1

Phenotype: short stature, low tone, small hands and feet, mild to moderate developmental disability, hypogonadism, obesity
Interitance pattern: 70% of the time it is from new deletion of the paternally derived chrom, 30% of the time uniparental disomy
genetic characteristics: imprinting problem. lack of expression of the paternal allels of genes on chrom 15

Front 2

Angelman Syndrom
phenotype:
Inheretance:
genetic characteristics:

Back 2

phenotype: severe mental retardation, seixures, poor speach developement and ataxic gait
Inheretance:lack of expression or function of the maternally inherited UBE3A gene allele. so it is paternally inhereted only
genetic characteristics: 68% new deletion, 7% uniparent disomy

Front 3

What are 4 "common" repeat expansion diseases?

Back 3

Fragile X syndrome of mental retardation
Myotonic dystrophy 1 and 2
Huntington’s disease 1 and 2
Spinocerebellar ataxia

Front 4

Myotonic Dystrophy type 1
phenotype:
Inheretance:
genetic characteristics:

Back 4

phenotype:muscular weakness, myotonia, facial hypotonia, cardiac arrhythmias, presenile cataracts, endocrinopathy (impaired glucose tolerance), dysphagia
Inheretance:Autosomal dominant with anticipation
genetic characteristics:CTG repeat length ranges Normal 5 - 30
Affected ~ 50 - > 2,000

Front 5

In myotonic dystrophy 1 and 2

Back 5

CCUG & CUG-rich RNAs dysregulate splicing in nucleus to cause dz

Front 6

Fragile X syndrome
phenotype:
Inheretance:
genetic characteristics:

Back 6

most common hereditary form of mental retardation
phenotype:mild physical phenotype, moderate to sever mental retardation
Inheretance:unusual X-linked pattern of inheritance = the so-called
“Sherman paradox” of anticipation
genetic characteristics:

Front 7

Where is the "fragile x" spot?

Back 7

on X chrom q27

Front 8

What is the Molecular basis of fragile X syndrome?

Back 8

Expansion of the CGG repeat leads to decreased mRNA levels and decreased levels of the FMR-1 protein.
loss of funtion of the FMR-1 protein

Front 9

what is fragile X-associated tremor-ataxia syndrome ?

Back 9

research revealed a trimodal allele distribution: premutation carriers have intermediate expansions of 55 - 200 CGG repeats. a syndrome of progressive intention tremor, ataxia, and parkinsonism was described in elderly male premutation carriers

Front 10

What are the diagnostic featurs of fragile X-associated tremor-ataxia syndrome?

Back 10

display tremor or ataxia, and often have cognitive impairment and/or memory loss
brain atrophy

Front 11

Do FRAXA patients develop FXTAS
signs or symptoms with age?

Back 11

NO

Front 12

FXTAS is a

Back 12

RNA gain-of-function disease

Front 13

Huntington's Disease
Phenotype:
Inheretance:
Genetic characteristics:

Back 13

Phenotype:Progressive movement disorder = choreiform (dance-like) movements
Behavioral abnormalities and psychosis, Intellectual decline; progressive impairment; death 10-20 yrs after onset
Inheretance:Autosomal dominant disorder (adult onset ~38) with anticipation
Genetic characteristics: CAG repeats, Premutation range is 27-36 CAG repeats, but only very rarely expands into full mutation range

Front 14

Spinocerebellar Ataxias
Phenotype:
Inheretance:
Genetic characteristics:

Back 14

Phenotype:
Inheretance:autosomal dominant with anticipation (worsening of disease phenotype in successive generations)
Genetic characteristics:

Front 15

Wolf-Hirschhorn Syndrome (4p-)
Phenotype:
Inheretance:
Genetic characteristics:

Back 15

Phenotype:Growth retardation, with abnormal facies.Cardiac, renal, and genital abnormalities. No movement abnormalities.
Inheretance:
Genetic characteristics:The Human “Knockout” of the Huntington Locus. Proves that HD is a gain of function problem

Front 16

In general CAG repeat expansions are gain-of-function or loss-of-function?

Back 16

gain of function

Front 17

What are 3 RNA gain-of-function disorders

Back 17

DM1, DM2, FXTAS

Front 18

What are 3 CAG / polyglutamine disorders ?

Back 18

HD, spinocerebral ataxia

Front 19

What is 1 Loss-of-function disorders ?

Back 19

fragil x

Front 20

What is Mitochondrial Heteroplasmy?

Back 20

Children of an affected mother can escape inheriting a mitochondrial disorder, or express different features to variable degrees, depending upon how the mutation is distributed within the population of hundreds of mitochondria inherited from the oocyte and the population distribution within a specific tissue in the body. Similarly, an unaffected mother could conceivably have affected children. It offers an explanation for incomplete penetrance in a mitochondrial disorder.

Front 21

What are the three ways to activate proto-ongogenes?

Back 21

point mutation
chromosomal translocation
gene amplification

Front 22

Oncogenes are dominant at the _____ level

Back 22

cellular

Front 23

Oncogene mutations are Mutations are ______ and (almost) never inherited

Back 23

somatic

Front 24

With Tumor suppressor genes:
_______must be inactivated in order to cause cancer

Back 24

Both alleles

Front 25

Tumor suppressor genes are normal genes whose _______ can lead to cancer

Back 25

ABSENCE

Front 26

p53 is a tumor suppressor or oncogene?

Back 26

tumor suppressor

Front 27

What happens to p53 in Li-Fraumeni Syndrome?

Back 27

mutated in the germline. inherited autosomal dominant. Somatic event can lead to loss of heterozygosity

Front 28

Li-Fraumeni Syndrome causes

Back 28

inheritance of multiple malignancies, esp. breast cancer, soft tissue sarcoma, osteosarcoma, brain tumors, leukemia, and adrenocortical carcinoma

Front 29

The likelyhood of developing Retinoblastoma with 1 germline mutation is ____
with 0 germline mutations is ______

Back 29

about 100%
about 1 in a million

Front 30

What is RetinoblastomaContiguous Gene Deletion Syndrome?

Back 30

Facial AppearanceProminent eyebrows, broad nasal bridge, bulbous tip of nose, large mouth with thin upper lip, long philtrum
Mental Retardation
Small Stature

Front 31

What is contiguous gene deletion syndrome?

Back 31

A syndrome caused by a microdeletion that spans two or more genes tandemly positioned along a chromosome. Microdeletion is often too small to be visualized using conventional cytogenetic techniques; detection often requires fluorescent in situ hybridization (FISH).

Front 32

What is von Hippel-Lindau Syndrome?
How is it inherited
phenotype
genetics

Back 32

How is it inherited: Autosomal dominant, incidence 1:36,000

phenotypeHemangioblastoma of brain, hemangioma of retina, pheochromocytoma, renal cell Ca

genetics:VHL gene encodes protein involved in response to hypoxia

Front 33

Familial Adenomatous Polyposis
How is it inherited
phenotype
genetics

Back 33

How is it inherited: autosomal dominante
phenotype
genetics: APC (5q21) encodes cytoplasmic protein involved in WNT signaling

Front 34

What are the Hallmarks of familial breast cancer?

Back 34

1. Younger age of onset
2. Bilateral or multifocal occurrence of cancer.
3. Ovarian cancer in the family.
4. Male breast cancer.

Front 35

Tumor supressor genes are _______ at the cellular level, but ______ at the systems level

Back 35

Recessive at the cellular level: both alleles must be inactivated

dominant:Identified as genes responsible for autosomal dominant human cancer predisposition syndromes

Front 36

Ataxia Telangiectasia
inheretance
phenotype
genetics

Back 36

inheretance: Autosomal recessive
phenotype: Cerebellar ataxia, conjunctival telangiectasias, increased risk for malignancy (esp. leukemia and lymphoma)

genetics: Malignancy risk ~40%

Front 37

Fanconi Anemia

Back 37

Short stature, radial ray limb defects, abnormal pigmentation, developmental delay
Autosomal recessive
Bone marrow failure
Increased risk of leukemia and solid tumors (developing at an average age of 23yo)
Genetically heterogeneous—13 complementation groups

Front 38

Hereditary Nonpolyposis Colon Cancer is caused by

Back 38

DNA mismatch repair, Penetrance is usually age related.
incompletely penetrant. So not all individuals who carry these mutations will get colorectal cancer, but the risk increases as individuals age
can get multipe types of cancer

Front 39

What are the mismatch repair genes in Hereditary nonpolyposis colon cancer?

Back 39

MSH2, MSH6, MLH1, PMS2

Front 40

30-40% of all colorectal cancers display ____________

Back 40

microsatellite instability

Front 41

Rare alleles in our population lead to __________Mendelian cancer syndromes
Common alleles in our population lead to ____________ cancer susceptibilities

Back 41

high-penetrance

moderate-to-low-penetrance

Front 42

Characteristics of G-light and G-dark Bands

Back 42

G light:Contain GC-rich DNA
Early-replicating
Contain most genes

G Dark:Contain AT-rich DNA
Late-replicating
Contain few genes

Front 43

What are the three etiologies of Down syndrom.

Back 43

1. Trisomy 21 (95%)
-nondisjunction (maternal, meiosis I)
-associated with AMA
2. Robertsonian translocation (2-4%)
3. Mosaicism (1-3%)
- trisomic conception followed by loss of extra chromosome in some cells during mitosis (trisomy rescue)

Front 44

Edwards Syndrome (Trisomy 18)
phenotype:
prognosis:

Back 44

phenotype:
Prenatal growth deficiencyUnique facial featuresDistinctive hand abnormalityCHDDiaphragmatic HerniaSevere MR

prognosis:
~50% mortality by 1 month
~10% alive by 1 year

Front 45

Patau Syndrome (Trisomy 13)
phenotype:
prognosis:

Back 45

phenotype;
CNS malformations (holoprosencephaly)Cleft lip/palateMicrophthalmiaPolydactylyCutis aplasia
prognosis: bad