Day 1, Lecture 3: Genetics: Organization of Human genome

Question 1

__% of all live born neonates have a significant genetic disease

Answer 1

3%

Question 2

___% of all causes of infant mortality in the U.S. is due to genetic disease

Answer 2

20%

Question 3

____% of all pediatric hospital admissions have a clearly defined genetic disease

Answer 3

5-10%

Question 4

Types of Genetic disease

Answer 4

Question 5

Disease caused by interaction of multiple genes +/- environmental factors

Answer 5

Multifactorial/polygenic disease

Question 6

Cystic fibrosis and Sickle cell disease are examples of what type of genetic disease

Answer 6

Single gene defect

Question 7

Common congenitla defects {NTDs, congential heart disease} are examples of what type of genetic disease

Answer 7

Multifactorial/Polygenic Disease

Question 8

Leber hereditary optic neuropathy (LHON) is an example of what type of genetic disease

Answer 8

Mitochondrial Disorders

Question 9

Nuclear DNA is packaged into _____

Answer 9

chromosomes

Question 10

Only ____% of the entire genome is used for encoding proteins

Answer 10

1-2%

Question 11

How many mitochondrial genes are there

Answer 11

37

Question 12

there are about how many genes in the nuclear genome

Answer 12

25,000 genes

Question 13

what percent of the nuclear genome is genes

Answer 13

• 35%
  
  • of which only about 5% codes for proteins (about 1-2% of entire genome)
  • of which about 95% is non-coding DNA

Question 14

What percent of the nuclear genome is extragenic DNA

Answer 14

• About 65%
  
  • of which about 60% is unique or low copy Number repeat DNA
  • of which about 40% is moderate to highly repetitive DNA

Question 15

DNA is an _____ double helix

Answer 15

anti-parallel

Question 16

DNA is ___ handed. Explain?

Answer 16

• Right handed
  
  • turns clockwiss as it goes away from you

Question 17

How many base pairs are there per turn of the DNA double helix

Answer 17

10 base pairs

Question 18

Question 19

_____ is the repeating unit fo DNA

Answer 19

• Nucleotide

Question 20

Question 21

DNA replication is ___-conservative

Answer 21

semi-conservative

Question 22

Question 23

DNA is replicated in the ____ direction

Answer 23

• 5’ to 3’

Question 24

DNA replication is ____-discontinuous. Meaning

Answer 24

• semi-discontinuous.
  
  • The leading strand is replicated continuously and the lagging strand is replicated discontinuously

Question 25

Transcription occurs in the _____ direction

Answer 25

5' to 3' direction (thus it uses the template strand (antisense strand) to make the sense sense strand)

Question 26

\_\_\_\_ is the fundamental unit of DNA packaging

Answer 26

* Nucleosome * Nucleosome is made of 8 histone proteins

Question 27

The nucleosome is the fundamental unit of DNA packaging. It is composed of 8 histone proteins around which ___ bp of DNA is coiled ___ turns

Answer 27

146 bp of DNA is coiled 1.75 turns

Question 28

The kinetochore is present at the centromere; and is the site for microtubule spindle attachment for chromosome segregation during cell division

Answer 28

kinetochore

Question 29

The central function of the centrosome is to

Answer 29

house the kinetochore

Question 30

\_\_\_\_ is the most widely used technique for studyign mammalian chromosomes

Answer 30

G-banding

Question 31

Aneuploidy

Answer 31

* can't be divided by 23 * note that most chromosomal aneuploidies are in the smaller autosomal chromosomes such as chromosome 21

Question 32

Examples of anueploidy

Answer 32

* Trisomy 21 (Down Syndrome): 47, XX, +21 * Turner Syndrome: 45, X * Klinefelter Syndrome: 47, XXY

Question 33

What is Reciprocal Translocation?

Answer 33

* Reciprocal translocations are usually an exchange of material between nonhomologous chromosomes. * Estimates of incidence range from about 1 in 500. * Such translocations are usually harmless and may be found through prenatal diagnosis. * However, carriers of balanced reciprocal translocations have increased risks of creating gametes with unbalanced chromosome translocations, leading to miscarriages or children with abnormalities.

Question 34

Telomere structure and function

Answer 34

Question 35

Telomere length is maintained by \_\_\_\_\_

Answer 35

Telomerase

Question 36

Telomeres shorten by ___ bp per cell division (eventually leading to \_\_\_)

Answer 36

100 bp per cell division (eventually leading to senescence)

Question 37

Major Classes of repetitive DNA

Answer 37

Question 38

What is DNA polymorphism?

Answer 38

* if a change in the genetic sequence (at a specific location) is present at a frequency of at least 1% in the population * Single nucleotide polymorphism (SNP) * Variation at a specific single nucleotide * polymorphic microsatellite repeats * Copy number variations (CNV)

Question 39

Copy Number Variations (CNV)

Answer 39

* Large segments of DNA * ​10kb-5Mb * about 12% of the genome (about 1500) * a type of polymorphism * Deviations from the normal expected chromosomal make up. Microdeletions or micro- duplications detected by chromosomal microarray are such examples. Identied CNVs are classied as known benign, known pathogenic, or of unknown clinical signicance. Copy number variant is now the preferred term over “copy number change.”

Question 40

Epigenetic modification is a mechanism of \_\_\_\_\_

Answer 40

* genome defense

Question 41

can tandem repeats be polymorphic?

Answer 41

* Yes * Single Nucleotide Polymorphism (SNP) * Polymporphic microsatellite repeats * Copy Number Variations (CNV)

Question 42

Can interspersed repeats transpose

Answer 42

* Yes * Ex. L1 repeats and Alu repeats

Question 43

Epigenetic modification of the genome

Answer 43

* Chemical modication of histones determines transcriptional activity of genes- this represents functional organization of the genome * DNA is methylated at CpG dinucleotides

Question 44

Euchromatin

Answer 44

* Most of the DNA in interphase nuclei; in extended, active form * Open chromatin * Acetylated and unmethylated histone tails * No DNA methylation * at actively expressed genes (functional regulation)

Question 45

Heterochromatin

Answer 45

* Highly condensed, compact, transcriptionally inactive DNA * Deacetylated and Methylated histone tails * Methylated DNA * Seen at repetitive DNA (defense) * Constitutive * always inactive (1q, 9q, 16q) * Facultative * either active/ inactive form (X inactivation)

Question 46

The protruding N-Terminal Tails are present on which histones

Answer 46

* H3 * H4

Question 47

DNA is methylated at \_\_\_\_

Answer 47

* CpG dinucleotides (5'-CG-3') * Methylation at the 5 carbon of cytosine only if it si followed by a guanine in the DNA backbone * 70% of the CpG sites in the human genome are methylated * 15% of the CpG sites are concentrated in unmethylated CpG

Question 48

\_\_\_% of the CpG sites in the human genome are methylated

Answer 48

70%

Question 49

\_\_\_% of the CpG sites are concentrated in unmethylated CpG

Answer 49

15%

Question 50

Question 51

Question 52

Gene

Answer 52

A unit of heredity. A gene refers to a specific segment of DNA that can be delineated by a start and stop position. Genes typically code for a speci c product (oftentimes a protein molecule).

Question 53

Nucleosome

Answer 53

The basic unit of DNA packaging. It comprises a short length of DNA wrapped around a core of histone proteins.

Question 54

Nucleotide

Answer 54

The basic unit of DNA and RNA. Nucleotides are composed of a nitrogenous base, a 5-carbon sugar (either ribose or 2-deoxyribose), and a phosphate group.

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