Lecture 1

Question 1

Genetic disorders account for ….. of all:

childhood blindness, childhood deafness, severe MR

Answer 1

50%

Question 2

Genetic disorders / CA account for…. of all childhood hospital admissions

Answer 2

30%

Question 3

Genetic disorders / CA account for … of all childhood deaths

Answer 3

40-50%

Question 4

….. of the population (by age 25 years) have a disorder

in which genetic factors play a role

Answer 4

5 - 8%

Question 5

….. of all malignancy is directly due to genetic factors

Answer 5

1 %

Question 6

….. of common cancers have a strong genetic component

Answer 6

10 %

Question 7

Chromosome disorders

Answer 7

Loss of tiny amount of
chromosome material molecular cytogenetics (FISH),
microarray CGH.

Question 8

Age of expression of chromosomal disorders

Answer 8

1st trimester

Question 9

Age of expression of single gene disorders

Answer 9

At delivery but also LATE ONSET (20s/30s)?

Question 10

Single gene disorders that increase in adulthood (late onset) are …

Answer 10

Huntingtonschorea

myotonic dystrophy

Question 11

Genome

Answer 11

the totality of an organism`s DNA

Question 12

Human Genome

Answer 12

a set of instructions for construction and

management of human body

Question 13

Euchromatin

Answer 13

forms the main body of the
chromosome and has a relatively high density
of coding regions or genes.

Question 14

Heterochromatin is

Answer 14

chromatin that is either

devoid of genes or has inactive genes

Question 15

Heterochromatin eg..

Answer 15

Constitutive

Facultative (Barr body)

Question 16

how much of our DNA actually encodes

proteins

Answer 16

< 2%

Question 17

Special features of chromosomes

Answer 17

Euchromatin
Heterochromatin
Centromere
Telomeres

Question 18

Centromere

Answer 18

facilitate separation

Question 19

Telomeres

Answer 19

facilitate DNA replication

process

Question 20

House keeping genes

Answer 20

20% of genes
Transcribed in ALL cells of the body
Encode products required for cell MAINTENANCE AND METABOLISM

Question 21

Tissue – specific

genes)

Answer 21

80% of the genes 
Transcribed only in SPECIFIC TISSUES AT SPECIFIC TIME
In most cells only
a small proportion of genes are actively
transcribed even though all have exactly
the same DNA sequence.

Question 22

gene

Answer 22

Fundamental unit of heredity

Question 23

“Structural” gene

Answer 23

gene that codes for a
protein product Sequence of DNA that can be
translated to protein

Question 24

Single copy DNA

Answer 24

45% of genome

Question 25

Repetitive DNA

Answer 25

55% of genome

Question 26

Divisions of Repetitive DNA

Answer 26

Satellite and Dispersed DNA

Question 27

Satellite DNA

Answer 27

Alpha- tandem repeats in centromeres Minisatellite- tandem repeats Microsatellite- "

Question 28

Dispersed DNA

Answer 28

SINEs- short interspersed repeated sequences | LINEs- long repeated sequences

Question 29

Variation

Answer 29

a change in genetic | material

Question 30

Mutation

Answer 30

disease –causing variation of a single gene (DNA sequence) or chromosomes

Question 31

Alleles

Answer 31

the differing DNA | sequences among individuals

Question 32

Polymorphism

Answer 32

``` > 2 alleles, each having a frequency that exceed 1% of the population. They can be normal variations or rarely disease-causing alleles ```

Question 33

Gene size effect on mutation rates

Answer 33

- large genes are more likely | mutation hotspots - methylated CG to TG

Question 34

Mutations in genes can occur | because of

Answer 34

* DELETIONS * INSERTIONS * DUPLICATIONS * SUBSTITUTIONS * GENE FUSION * AMPLIFICATIONS

Question 35

DELETIONS

Answer 35

``` • uncommon • indicated by the absence / altered size of a DNA fragment ```

Question 36

examples of DELETIONS

Answer 36

``` Thalassemia Cystic Fibrosis DMD/BMD Growth hormone deficiency Familial hypercholesterolemia ```

Question 37

Alpha Thalassemia

Answer 37

``` The loss of 1 or 2 of these genes has no clinical effect The loss of all 4 (Southeast Asians) leads to hydrops fetalis (stillbirth or neonatal death) The loss of 3 of these genes leads to moderately severe anemia. ```

Question 38

DUPLICATIONS

Answer 38

``` Charcot-Marie-Tooth disease type 1A mis-pairing between homologous DNA sequences in close proximity ```

Question 39

INSERTIONS

Answer 39

``` Hemophilia - insertion of a LINE in the factor VIII gene Neurofibromatosis - insertion of an Alu ( SINE) sequence ```

Question 40

SUBSTITUTIONS

Answer 40

``` most common cause of mutagenesis in the human genome Sickle cell anemia Phenylketonuria  Thallassemia ```

Question 41

Gene fusion

Answer 41

``` Hemoglobin Lepore Red / green color blindness Unequal crossing over ```

Question 42

deuteranopia

Answer 42

) Unequal cross-over can produce a green dichromat with no green genes -

Question 43

red dichromat - protanopia or a green anomalous trichromat - deuteranomaly. produced by..

Answer 43

Unequal cross-over that occurs within the red and green genes

Question 44

protanomaly

Answer 44

Cross-over within the red and green genes can also produce red anomalous trichromats -

Question 45

AMPLIFICATIONS | expanded repeats

Answer 45

Increase in size of repeat DNA sequences normally present within or near certain genes

Question 46

AMPLIFICATIONS eg...

Answer 46

Fragile X syndrome Huntington disease Muscular dystrophy Friedreich ataxia

Question 47

Molecular Consequences of | Mutation

Answer 47

A Gain of Function of the protein product some AD disorders. A mutation resulting in a novel protein, over-expression or inappropriate expression of a protein such that there is an added or increased function of the mutant protein McCune-Albright syndrome Charcot-Marie-Tooth disease;

Question 48

McCune - Albright syndrome

Answer 48

polyostotic fibrous dysplasia (bone lesions), cafe au lait spots (skin lesions), and hyperfunction of several endocrine glands (precocious puberty, hyperthyroidism, pituitary gigantism, or Cushing's syndrome)