Human Genome And Chromosomes

Front 1

What is the importance of genomic medicine

Back 1

Understanding:

- Genome structure

- Genome biology

- Disease biology

Advancing science in medicine

Improving effectiveness of healthcare

Front 2

Name the overall parts of the human genome

Back 2

Nuclear genome

Mitochondrial genome

Front 3

What are the main features of the human nuclear genome?

Back 3

- 3.2 x 10^9 base pairs

- ~21,000 protein coding genes

- 46 chromosomes

-Inherited from both parents

Front 4

What are the main features of the human mitochondrial genome?

Back 4

- 16.6 x 10^3 base pairs

- 13 protein coding genes

- 1 circular DNA molecule

- Maternally inherited

Front 5

At which stage of mitosis are all 46 chromosomes most clearly seen?

Back 5

Metaphase

(IPMAT + Cytokinesis)

Front 6

What are Karyotype?

Back 6

The number and visual appearance of chromosomes in the cell nuclei of an organism or species.

To arrange and classify chromosome complement of an an organism based on number, size, shape and other chromosomal characteristics.

Front 7

What staining is most commonly used to view chromosome Karyotypes?

Back 7

Giemsa dye

Front 8

How are chromosomes prepared for viewing under the microscope?

Back 8

Cells are arrested during cell division using a colchicine solution (prevents microtuble polymerization so spindles can be arrested).

Front 9

How are chromosomes stained for viewing under the microscope?

Back 9

Chromosomes treated with trypsin (denatures proteins)

and stained with Giemsa dye

Front 10

Name the technique most commonly used in cytogenetics to produce a visible Karyotype by staining condensed chromosomes

Back 10

G-banding / Giemsa banding

Front 11

At which stage of the cell cycle are chromosomes easily viewed in their Karyotypes?

Back 11

Metaphase of mitosis

Front 12

What's key to preparing cells for chromosomal viewing under the microscope?

Back 12

Disruption of spindle fibres and arresting the cell in a state of metaphase

Front 13

Name the 6 parts of a chromosome (as view with Giemsa staining)

Back 13

G-light band

G-dark band

Telomere

Centromere

p (short arn)

q(long arm)

Front 14

Characteristics of a G-light band

Back 14

Gene-rich

G-C base pairs rich

Early replicating

Front 15

Characteristics of a G-dark band

Back 15

Gene poor

A-T base pairs rich

Late replicating

Front 16

Role of the Telomere

Back 16

Protective DNA and protein "cap"

Repetitive DNA

Front 17

Role of the Centromere

Back 17

Keeps sister chromatids together

Attaches sister chromatids to microtubules

Repetitive DNA

Front 18

Number of chromosomes in a human nucleus

Back 18

46 (23 pairs), one of each pair is inherited from a parent

Front 19

How many autosome chromosome pairs?

Back 19

22

Front 20

How many sex chromosome?

Which is for which gender?

Back 20

1 (pair n23)

XX - female

XY - male

Front 21

Haploid number

Back 21

23

(Haploid = cells containing only one complete set of chromosomese e.g. gametes).

Front 22

Diploid number

Back 22

46

(Diploid = cells that have two sets of chromosomes, paternal+maternal e.g. somatic cells)

Front 23

What is Aneuploidy?

Back 23

Denotes an abnormal number of chromosomes

Front 24

What makes up a chromosome?

Back 24

DNA

Histone

Other proteins

Front 25

Gene vs. disease:

Give 4 genes which cause disease, and their chromosome pair number.

Back 25

LCT: Lactose deficiency (2)

HTT: Huntigdon disease (4)

HEXA: Tay-Sachs disease (15)

BTK: X-linked primary immune deficiency (X)

Front 26

How are genes organised along each chromosome?

Back 26

In a linear order

Front 27

Describe the term "Coding Sequence"

Back 27

Section of DNA that encode proteins

Front 28

Describe the term "Non-Coding Sequence"

Back 28

Intergenic regions and introns;includes control elements and functional RNAs e.g. microRNA and long non-coding RNAs

Front 29

Describe the term "Exon"

Back 29

regions of genes that encode protein sequences

Front 30

Describe the term "Introns"

Back 30

non-coding regions between exons in genes

Front 31

Describe the term "Control elements"

Back 31

sequences that regulate transcription i.e. promoters and enhancers

Front 32

Describe the term "Pseudogene"

Back 32

non-functional copy of a gene; arises from gene duplication then deleterious mutation in one copy.

Front 33

Describe the term "repetitive Sequences"

Back 33

tandem repeats of closely related DNA sequences

Front 34

What percentage of DNA are Conding Sequences?

Back 34

1.6%

Front 35

What percentage of DNA are Repetitive sequences?

Back 35

~ 40%

Front 36

Name the 3 steps of the process that starts with DNA and ends with the synthesis of a protein.

Back 36

Transcription (DNA to Pre-mRNA)

Splicing (Pre-mRNA to RNA)

Translation (mRNA to Protein)

Front 37

Where are control elements of transcription contained?

Back 37

In the Non-coding sequences

Front 38

Explain the action of the control elements

(Enhancer - chromatin Looping - Promoter - Splicing signals)

Back 38

Transcription factors bind to promoter site (starting at TATA box);

Section of transcription factor binds to the enhancers (upstream from promoters), this increases rate of transcription;

This action loops the chromatin section between the enhancer and promoter;

Splicing signals indicate where splicing occurs

Front 39

How many protein-coding genes are there?

Back 39

19,942

Front 40

How many Long non-coding RNA genes are there?

Back 40

14,470

Front 41

How many small non-coding RNA genes are there?

Back 41

9,519

Front 42

How many Pseudogenes are there?

Back 42

14,363

Front 43

Define the term: Disomy

Back 43

Two copies of a chromosome

Front 44

What gene is "LCT" and on which chromosome is it found?

Back 44

Lactoce deficiency

Chromosome 2

Front 45

What gene is "HTT" and on which chromosome is it found?

Back 45

Huntingdon disease

Chromosome 4

Front 46

What gene is "HEXA" and on which chromosome is it found?

Back 46

Tay-Sachs disease

Chromosome 15

Front 47

What gene is "BTK" and on which chromosome is it found?

Back 47

BTK

X-linked primary immune deficiency

Front 48

Define the terms used to denote normal variation in chromosome number and structure

Back 48

HAPLOID (23 Chromosome n.)

DIPLOID (46 Chromosome n.)

DISOMY (two copies of a chromosome)

Front 49

Define the terms used to denote Aneuploidy/abnormal variation in chromosome number and structure

Back 49

POLYPLOIDY (gain of +1 haploid chromosome ses) e.g. Triploid, Tetraploid

MONOSOMY - one copy of a chromosome

TRISOMY - three copies of a chromosome

TETRASOMY - four copies of a chromosome

Front 50

Define the term Polyploidy

Back 50

gain of one or more haploid chromosome sets

Front 51

Define the term Tri/Tetraploid

Back 51

three/four haploid sets

Front 52

Define the term Mono/Tri/Tetrasomy

Back 52

one/three/four copies of a chromosome

Front 53

What are the 4 abnormalities observed in Chromosome structure?

Back 53

Deletion

Duplication

Inversion

Translocation

Front 54

Define the term chromosomal Translocation

Back 54

Joining part of one chromosome to a second chromosome.

Front 55

State the benefit of reciprocal chromosomal translocation

Back 55

Part of the second chromosome joins the first chromosome, no net loss or gain of material

Front 56

State the name given to the action of two chromosomes joining at their centromere

Back 56

Robertsonian Translocation

Front 57

State the benefit of a Karyotype

Back 57

Helping identify chromosome abnormalities that are evident in either structure or number of chromosomes.

Front 58

State the two types of chromosomal translocation

Back 58

Reciprocal translocation

Robertsonian translocation

Front 59

How can you observe tranlocations in brain tumour?

Back 59

Through fluorescent dyeing of the chromosome;

each homologous pair should be of the same fluorescent colour unless translocation has occured.

Front 60

Name 3 most common autosomal numerical abnormalities in liveborn babies

Back 60

Down syndrome

Edwards syndrome

Patau syndrome

Front 61

Name two common sex chromosome numerical abnormalities in liveborn babies

Back 61

Turner syndrome

Klinefelter syndrome

Front 62

Name the most common all chromosome numerical abnormality in liveborn babies

Back 62

Triploidy (69 chromosomes)

Front 63

What aneuploidy is observed in Down Syndroms' sufferers?

Back 63

Trisomy 21 (the 21st chromosome has three copies)

Front 64

Give the characteristics of Down Syndrome sufferers

Back 64

Affects 1 in 700 live births

>60% spontaneously aborted

20% stillborn

Distinct facial apprearance

Marked muscle hopotonia (decr. tone) as baby

may have 1 palmar crease

Learning difficulty (IQ <50)

Congenitall heart malformations (40%)

Front 65

What percentage of Down syndrom patients are still born?

Back 65

20%

Front 66

What percentage of Down syndrom patients are spontaneously aborted?

Back 66

>60%

Front 67

What's the ratio of live births that result in Down Syndrome babies?

Back 67

1 in 700

Front 68

What is the usual IQ of Down Syndrome sufferers?

Back 68

<50

Front 69

What percentage of Down Syndrome sufferers have congenital heart malformations?

Back 69

40%

Front 70

State the thre known chromosomal patterns of Down Syndrom

Back 70

Trisomy 21

Extra copy of c21 because of Robertsonian translocation

Mosaicism with normal and trisomy 21

Front 71

Define the term "Mosaicism"

Back 71

property or state of being composed of cells of two genetically different types (within the same organism)

Front 72

State the advantage conferred by mosaicism with normal and trisomy 21 in Down Syndrome patients

Back 72

Much milder features due to the presence of the normal cells.

Front 73

When does mosaicism with normal and trisomy 21 occur in Down Syndrome patients?

Back 73

postzygotically

Front 74

What percentage of Down syndrom patients have trisomy 21?

Back 74

95%

Front 75

What percentage of Down syndrom patients have an extra copy of chromosome 21 because of Robertsonian translocation?

Back 75

4%

Front 76

What percentage of Down syndrome patients have mosaicism with normal and trisomy 21 cell lineages?

Back 76

1%

Front 77

What is the association between Trisomies and maternal age?

Back 77

Possitive correlation

in Down Syndrome sufferers

Front 78

Give 2 possible explanation for the association of trisomies and increased maternal age in Down Syndrome sufferers

Back 78

- Eggs help at crossing-over stage (meiosis) for approx. 6 months getstation

- "wear and tear" in the cell division machinery, with increasing maternal age

Front 79

State the characteristics of Edwards Syndrome

Back 79

Trisomy 18 (three n.18 chromosomes)

affects 1 in 3000 births

Multiple malfomations (esp. heart and kidneys)

Clenched hands with overlapping fingers

Front 80

What ratio of live birth is attributed to Edwards Syndrome?

Back 80

1 in 3000

Front 81

State the characteristics of Patau syndrome

Back 81

Trisomy 13 (three n.13 chromosomes)

Affects 1 in 5000 births

Multiple malformations

Affects midline structures, esp. incomplete lobation of brain; cleft lip; congenital heart disease

Front 82

What particular signs are present in Patau Syndrome sufferers?

Back 82

Lobation of brain;

Cleft lip;

Congenital heart disease

Front 83

What ratio of births are affected y Patau Syndrome?

Back 83

1 in 5000

Front 84

What disease occurs as a result of Trisomy 18?

Back 84

Edwards Syndrome

Front 85

What disease occurs as a result of Trisomy 13?

Back 85

Patau Syndrome

Front 86

What disease occurs as a result of Trisomy 21?

Back 86

Down Syndrome

Front 87

State the Characteristics of Klinefelter Syndrome

Back 87

47, XXY (normaly there are 46 chromosomes and the last pair is either XX or XY)

Affects 1 in 1000 males

Infertility (atrophic testes do not produce sperm)

Poorly developed 2nd sexual characteristics in some (lack of testosterone)

Tall

Front 88

What is meant by the term atrophic?

Back 88

Wasting away of a normally developed organ or tissue due to degeneration of cells.

Front 89

State the characteristics of Turner SYndrome

Back 89

45, X (normally there are 46 chromosomes with the last pair being either XX or XY)

affects 1 in 5000 females

99% are lost spontaneously in pregnancy

Short stature

Primary amenorrhoea (ovariers involute before birth)

Front 90

Define the term primary amenorrhoea

In which chromosomal condition can it be observed?

Back 90

Absence of menstrual period even at puberty, due to absence of the uterus or ovaries, a genetic disorder or hormonal imbalance.

Turner syndrome

Front 91

Which sex chromosomal disease results in 99% of spontaneous abortions?

Back 91

Turner syndrome

Front 92

What is the prevalance of Klinefelter Syndrome?

Back 92

1 in 1000 males

Front 93

What is the prevalance of Turner Syndrome?

Back 93

1 in 5000 females

Front 94

What sex chromosomal disease arises from a 47, XXY aploidy?

Back 94

Klinefelter Syndrome

Front 95

What sex chromosomal disease arises from a 45, X aploidy?

Back 95

Turner Syndrome

Front 96

What is meant by the term congenital?

Back 96

Describes a condition that is recognised at birth or is believed to have been present since birth

(c.malformations include all disorders present at birth, genetic or environmental)

Front 97

What is meant by the term coarctation?

Back 97

congenital narrowing of a short segment of the aorta

Front 98

State the 4 main umbrella types of prenatal diagnosis for chromosoma; abnormalities.

Back 98

Amniocentesis

Chorionic villus sampling

Non-invasive techniques

Pre-impantation genetic diagnosis & screening

Front 99

Describe Amniocentesis

Back 99

Withdrawing fluid sample surrounding a foetus in the uterus by pearcing amneotic sac through the abdominal wall

Genetic testing of cells from amniotic fluid

Ultrasound guidance -- trans-abdominal sampling

15-18 weeks into pregancy

Front 100

Describe Chorionic villus sampling

Back 100

Genetic testing of tissue from the placenta (chorionic villi - villi that links to chorion to give maximum SA.V ratio)

Ultrasound guidance -- trans-abdominal, trans-cervical sampling

12-14 weeks

Front 101

Describe the non-invasive techniques of prenatal diagnosis

Back 101

For Down syndrome

Ultrasound imaging of nuchal translucency

performed 11-14 weeks into pregancy

Front 102

What is the Chorion?

Back 102

Embryonic membrane that totaly surrounds the embryo from the time of implantation

Front 103

Define the term: Nuchal Translucency scanning (NT scanning)

Back 103

Ultrasound screening test,

measures maximum thickness of the translucency between skin and soft tissue overlyig the cervical region of the spine of the foetus.

Incr. NT associated with increased risk of chromosomal abnormality and variety of structural abnormalities

Front 104

What is involved in Pre-implantation genetic diagnosis & screening?

Back 104

Embryos created through IVF (invitro fertilisation)

Genes check against genetic conditions

Front 105

Give the Characteristics of the X-chromosome

Back 105

1100 genes

X-inactivation (Lyonization) in early female embryonic development

So proteins synthesised from X-chromosme are same amount in male and female

Pseudoautosomal region of X-chromosome not inactivated - contain genes present in Y-chromosome, involved in delopment

Front 106

Describe the purpose of X-inactivation

Back 106

Ensuring each female somatic cell only has one functional chromosome, as in mate somatic cells

So same number of proteins synthesised from both.

Front 107

Why are pseudoautosomal regions of the X-chromosome not inactivated in female?

Back 107

Contain genes also present in Y-chromosome

Genes important in development

Would confer a selective disadvantage

Front 108

What is the name given to a inactivated X-chromosome?

Back 108

Barr Body

Front 109

Define Barr Body

Back 109

Inactive X-chromosome in female somatic cell, rendered inactive through Lyonization (discovered by Mary Lyon, english geneticist)

Front 110

Describe the process of X-inactivation

Back 110

Xist expressed;

Leads to chromatin changes and spacial reorganisation of the chromosome;

leads to transcriptional inactivation;

N.B: X-inactivation only reversed in germ cells

Front 111

What is Xist?

Back 111

Long non-coding RNA encoded in the X-Inactivation Centre (XIC) on the X-chromosome

Front 112

What is XIC?

Back 112

X-Inactivation Centre located on the X-chromosome

Front 113

State the characteristics of a Y-Chromosome

Back 113

Variable size, few genes, many repeat sequences;

Encodes "Sex Determining Region of the Y-chromosome" - SRY gene

SRY encodes a protein member of HMG group of transcription factors)

SRY = responsible for male sex determination

Other genes on Y-chromosome also important for male sex determination

Front 114

What encodes the SRY?

Back 114

Y-Chromosome

Front 115

State the role of the SRY

Back 115

encodes a protein that is a member of the HMG group of transcription factors

is responsible for male sex determination

Front 116

What are HMG?

Back 116

High-Mobitily-Group = chromosomal proteins involved in regulation of DNA-dependent processes i.e. transcrition, replication, recombination, DNA repair

Front 117

What does SRY stand for?

Back 117

Sex Determining Region of the Y-chromosome