Stein Lectures

Question 1

What is FISH?

Answer 1

Fluorescence in situ Hyrbidization: it is a cytogenic technique where a specific DNA probe bound to a fluorescent or radioactive isotope is created to hybridize with a samples DNA in order to detmermine if that DNA exists in the host

Question 2

What are the three basic types of FISH?

Answer 2

1. Repeat sequences: usually derived from telomeres or centrosomes
2. Single Copy DNA: usually isolated from a cloned DNA of a disease-causing gene or a fragment of DNA of known loction associated with a particular gene
3. Chromosome painting: a combination of many unique fragments of DNA along a chromomse so that the entire chromosome fluoresces

Question 3

What are contiguous Gene Syndromes?

Answer 3

regions in the genome with clusters of closely associated genes (when duplicated or deleted express a specific clinical symptom) whose normal functions are generally unrelated

Question 4

What is VCFS?

Answer 4

Velocardiofacial syndrome: 2nd most common syndrome known to humans resulting from a 3 MB deletion on chromosome 22. There is a wide variation of effects including: hypotonia, short stature, learning disabilities, cardiac anomolies

Question 5

What is William’s Syndrome?

Answer 5

It’s caused by a deletion of an Elastin (ELN) gene on chromososome 7, the symptoms include: blue sclera, gifted musical abilities, usually low IQ, Stellate Iris, renal anomalies, terrible math skills

Question 6

What type of inheritance pattern do mitochondrial genes have?

Answer 6

Matrilineal, none of the mitochondrial genes are given by the father, however, some mitochondrial disorders could be X-linked or autosomal since mitochondria rely on some nuclear genes

Question 7

What is homoplasmy?

Answer 7

When all of the mitochondria within a cell have the same genome, meaning they’re the same

Question 8

What is heteroplamy?

Answer 8

When there are two or more different mitochondrial genomes present in a cell.

In order for a cell to display dysfunction there must be about 85% of mutant mitochondria expressed

Question 9

What region of DNA is frequently used in forensics?

Answer 9

Hyperviable minisatellite regions

Question 10

Why is mitochondrial DNA espcially resilient to long term degradation?

Answer 10

Because it is circular and their are multiple copies of it within each cell

Question 11

How is maternal serum alphafetoprotein useful?

Answer 11

MSAFP levels (high/low) have been associated with fetal abnormalities. Alpha fetoprotein is a major plasma protein produced by the yolk sac during fetal development. Several factors need to be calculated before the effect of this measurement is determined

High=Open spina bifida

Low=Down Syndrome

Question 12

When is ultrasound normally performed?

Answer 12

Around 18 weeks gestation

Question 13

What can you gather from an ultrasound?

Answer 13

Verify viability

Detect a multiple pregnancy

Determine gestational age

Determine Sex

Identify some abnormalities (clefting, nuchal translucency, neural tube deftects)

Question 14

What is alpha fetoprotein?

Answer 14

It is an albumin like protein produced by the fetal liver. It can cross the placenta into the maternal blood circulation.

Question 15

What is the maternal Quad test?

Answer 15

A serum assay measuring four different chemical concentrations of key molecules involved in fetal development

Question 16

What is cfpDNA?

Answer 16

cell free placental DNA. It is free floating DNA with placental/fetal origin. This can be analyzed to identify specific DNA sequences indicative of disease

Question 17

What is amniocentesis?

Answer 17

It is an invasive prenatal screening procedure whereby a needle is inserted through the abdomen into the amniotic cavity and amniotic fluid is withdrawn for testing. Risk of fetal loss is 1/200.

usually performed 16-18 weeks

Question 18

What can confirm an open neural tube defect, when hinted by elevated AFP levels?

Answer 18

The presence of Acetylcholinesterase which is found only in the neural tube

Question 19

Low AFP and karyotype analysis can confirm which common developmental disorder?

Answer 19

Down Syndrome

Question 20

What is Chorionic Villus sampling?

Answer 20

an invasive procedure in which the placenta is sampled as opposed to fetal tissue, both placenta and fetus are derived from teh original zygote and , thus, are usually biologically the same, but not always so an abnormal CVS could be a problem with just the placenta (amniocentesis could confirm)

Question 21

What is the adavantage of using CVS as opposed to Amniocentesis given it’s greater risk to the fetus?

Answer 21

It can be performed earlier 10-12 weeks gestation which can offer the possibility of more rapid and easier termination in the event of a severely affected fetus

Question 22

Explain clonality

Answer 22

The concept that a mutant cell line can be traced back to an original mutant cell line

Question 23

What type of tissue is affected in Sarcoma?

Answer 23

Mesenchymal (bone, muscle, fat, cartilage)

Question 24

What’s the difference between leukemia and lymphoma?

Answer 24

Both affect white blood cells:

Leukemia: bone marrow

Lymphoma: spleen/lymph nodes

Question 25

What tissue does carcinoma affect?

Answer 25

Epitheloid tissue (specialized immune system tissue)

Question 26

What's different about cancers arising from proto-oncogenes vs. tumor suppressor genes?

Answer 26

Proto-Oncogenes: **gain/change** of mutation (only **1 mutation required**) **Acquired** Tumor Suppressor: classical **recessive** (both losses required) **1** mutation may be **inherited** effect is an **accumulation of errors**, **inheritance** significantly **increases** **odds** of disease

Question 27

What is CML (Chronic Myelogenous Leukemia)?

Answer 27

A cancer from a **translocation** between chromosomes 9 and 22, results in a **chimeric** protein (**tyrosine kinase**), example of a **proto-oncogene**

Question 28

What is acute promyelitic leukemia?

Answer 28

proto-oncogene related disease where a translocation between chromosomes 15 adn 17 results in a defective, **FISH** confirmation is **required for diagnosis**

Question 29

What are retinoblasts?

Answer 29

They are precursor to retinal cells in the eye, in retinoblastoma these cells can acquire mutations leading to blindness or dangerous tumors of the eye

Question 30

Explain what must occur in a somatic tumor gene suppressor mutation?

Answer 30

There must be **two mutations** of the same gene in the **same cell**, if this does occur it is typically at a **later onset** than the inherited disease

Question 31

What is the disease Li Fraumeni?

Answer 31

A **familial** cancer syndrome, resulting from a **p53** defect, it causes **multiple neoplasia**

Question 32

What are 4 main characteristics of breakage syndromes?

Answer 32

Recessive mutation Chromosomal Instability Susceptibility to cancer Defective **DNA repair mechanisms** (allows an accumulation of defective genes)

Question 33

What are microsatellites?

Answer 33

**Repeats** of 2, 3, or 4 nucleotides **highly polymorphic** in population Often used to **detect DNA repair defects** (they are sensitive to slippage) **Indirect test**

Question 34

What is a constitutional karyotype/genotype?

Answer 34

The original DNA and chromosome complement that originated in the zygote.

Question 35

What is Prader-Willi syndrome?

Answer 35

Common **microdeletion** syndrome of chromosome 15, can cause **obesity**, bad temper, hypergonadism, small feet/hands It appears the same as Angleman syndrome under karytype analysis Results from a **pat​ernal deletion** or **maternal upd**

Question 36

What is angelman syndrome?

Answer 36

It is a **microdeletion** syndrome of chromosome 15, causes **severe mental retardation** skinny, hyperactive, inappropriate laughter (happy puppet syndrome) Results from a **maternal deletion** or **paternal upd**

Question 37

What is uniparental disomy?

Answer 37

Inheritance of a chromosome or chromosomes from 1 parent to the exclusion of the other parent

Question 38

What is uniparental heterodisomy?

Answer 38

When one parents contributes both of their homologous chromosomes and none from the other parent are given to the offspring.

Question 39

What is uniparental isodisomy?

Answer 39

When one parent contributes a single chromosome duplicate to their offspring. This can be the result of a zygote rescue in the event of a nondisjunction which would have resulted in a monosomy

Question 40

What is genetic imprinting?

Answer 40

The differential modification of the maternal and paternal genetic contributions to the zygote resulting in the **differential expression** of parental alleles during development and in the adult Typically associated with **methylation** (deactivated genes) The normal methylation process involves uniformally methylating all gametes based on the sex of the parent so that offspring receive both a paternal and maternally methylated chromosome regardless of sequence.

Question 41

Which DNA residue is methylated in the process of DNA methylation?

Answer 41

Cytosine

Question 42

What's Rett Syndrome?

Answer 42

A **neurodevelopmental** disorder, mainly affects **females**, intellectual disability, motor function dirsupted, **MECP2** is involved: a **transcription factor** that can activate or repress transcription, normal function rquired for **maturation** of **nuerons** and normal **development**

Question 43

What is chromosomal instability?

Answer 43

It is a gain, loss or rearrangement of chromosomes

Question 44

What is the main function of the tumor suppressor gene Rb1?

Answer 44

Retinoblastoma 1 **Tumor Suppressor** controls progression from **G1 to S** deletion results in elimination of important mitotic checkpoint