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KROMOSOM 17 &

KROMOSOM 18

KELOMPOK 9

Rizqiani Amalia Kusumasari

Satrio Wicaksono

Samuel Sandy

Siti Ruqayyah

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CHARACTERISTICS

Chromosome 17 one copy inherited from each parent one of the

pairs

It is the largest human autosome

rich in protein coding genes, having the secondhighest gene density in the genome

Chromosome 17 spans about 79 million DNA buildingblocks (base pairs) and represents between 2.5percent and 3 percent of the total DNA in cells.

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Contd

Chromosome 17 likely contains between 1,200

and 1,500 genes. These genes perform a

variety of different roles in the body.

Ideogram

http://d/IKD%20KULIAH/bahan%20search/bahan%20kromosom%20genetika/Chromosome%2017%20-%20Genetics%20Home%20Reference_files/chr-17.jpeg

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Jenis-jenis kelainan terkait kromosom 17

acute promyelocytic

leukemia

Alexander disease

Amish lethal microcephalyAndersen-Tawil syndrome

Birt-Hogg-Dub syndrome

bladder cancer

breast cancer

campomelic dysplasia

Canavan disease

Carney complex

Charcot-Marie-Tooth

disease

common variable immune

deficiency

cystinosis

dermatofibrosarcoma

protuberans

Ehlers-Danlos syndrome

epidermolysis bullosa

simplex

epidermolysis bullosa with

pyloric atresia

familial atrial fibrillation

familial hemophagocytic

lymphohistiocytosis

Freeman-Sheldon

syndrome

frontotemporal dementia

with parkinsonism-17

galactosemia

glycogen storage diseasetype I

GRN-related

frontotemporal dementia

hereditary folate

malabsorption

hereditary neuralgic

amyotrophy

hereditary neuropathy with

liability to pressure palsies

hyperkalemic periodic

paralysis

hypokalemic periodic

paralysis

Job syndrome

Leber congenital

amaurosis

Li-Fraumeni syndrome

limb-girdle muscular

dystrophy

Miller-Dieker syndrome

mucopolysaccharidosis

type III

N-acetylglutamate

synthase deficiency

neuroblastoma

neurofibromatosis type 1

nonbullous congenital

ichthyosiform erythroderma

nonsyndromic deafness

osteogenesis imperfecta

pachyonychia congenita

paramyotonia congenita

Pompe disease

pontocerebellar hypoplasia

potassium-aggravated

myotonia

progressive supranuclear

palsy

pyridoxal 5'-phosphate-

dependent epilepsy

short QT syndrome

Smith-Magenis syndrome

SOST-related sclerosing bone

dysplasia

spondylocostal dysostosis

tetra-amelia syndromeUsher syndrome

very long-chain acyl-CoA

dehydrogenase deficiency

vitiligo

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Genes on chromosome 17

ACADVL

ACTG1

ALOX12B

ALOXE3

ASPA

BRCA1

BRIP1

COL1A1

CTNS

ERBB2

FLCN

G6PC

GAA

GALK1

GFAP

GRN

GUCY2D

HES7

ITGB4

KCNJ2

KRT14

KRT16

KRT17

MAPT

MYH3

MYO15A

NAGLU

NAGS

NF1

NLRP1

PAFAH1B1PMP22

PNPO

PRKAR1A

RAI1

RARA

SCN4A

SEPT9SGCA

SGSH

SLC25A19

SLC46A1

SOST

SOX9

STAT3TNFRSF13B

TP53

TSEN54

UNC13D

USH1G

WNT3

YWHAE

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Changes in conditions of Chr-17

ACUTE PROMYELOCYTIC LEUKEMIA

caused by a rearrangement (translocation) of geneticmaterial between chromosomes 15 and 17 [t(15;17)]

fuses part of the PML gene from chromosome 15 withpart of the RARA gene from chromosome 17.

somatic mutationnot inherited.

The t(15;17) translocation is called a balanced

reciprocal translocation The protein produced from this fused gene is known as

PML-RAR.

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The RARA gene on chromosome 17 providesinstructions for making a transcription factor called theretinoic acid receptor alpha (RAR).

A transcription factor is a protein that attaches (binds)

to specific regions of DNA and helps control the activity(transcription) of particular genes.

Normally, the RAR protein controls the activity ofgenes important for the maturation (differentiation) ofimmature white blood cells beyond a particular stagecalled the promyelocyte.

The PML gene on chromosome 15 providesinstructions for a protein that acts as a tumorsuppressor, which means it prevents cells from growing

and dividing too rapidly or in an uncontrolled way.

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The PML protein blocks cell growth and division(proliferation) and induces self-destruction(apoptosis) in combination with other proteins.The PML-RAR protein interferes with the normal

function of both the PML and the RAR proteins.As a result, blood cells are stuck at thepromyelocyte stage, and they proliferateabnormally. Excess promyelocytes accumulate in

the bone marrow and normal white blood cellscannot form, leading to acute promyelocyticleukemia.

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Scheme ofacute promyelocytic leukemia

PML gene (chr-15) >< RARA gene (chr-17)[t(15;17) balanced reciprocal translocation]

PML-RAR

RARa protein tumorsuppressor

blood cells are stuck at the promyelocyte stage, and they proliferate

abnormally. Excess promyelocytes accumulate in the bone marrow and normal

white blood cells cannot form, leading to acute promyelocytic leukemia.

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MILLER-DIEKER SYNDROME

caused by a deletion of genetic material near the end of the

short (p) arm of chromosome 17.

signs and symptoms: are related to the loss of multiple genesin this region. The size of the deletion varies among affected

individuals.

The loss of a particular gene on chromosome 17, called

PAFAH1B1, is responsible for the syndrome's characteristic

sign of lissencephaly, a problem with brain development in

which the surface of the brain is abnormally smooth.

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another gene YWHAE, in the same

region of chromosome 17 increases the

severity of lissencephaly in people with Miller-

Dieker syndrome.

Additional genes in the deleted region

contribute to the varied features of Miller-

Dieker syndrome.

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Chromosome 18

one copy inherited from each parent, form one of

the pairs.

Chromosome 18 spans about 76 million DNA

building blocks (base pairs) and represents

approximately 2.7 percent of the total DNA in

cells.

CHARACTERISTICS

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Normal chromosome 18

Contd

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Major conditions changes in chr-18

18 p-

There is a missing piece from the short arm of

chromosome 18.

18q-

There is a missing piece from the long arm of chromosome 18. If the

missing piece is close to the centromere, it is called proximal 18q-. If the

missing piece is close to the end of the chromosome, it is called distal

18q-.

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Ring 18

One of the copies of chromosome 18 forms a ring, and material

is lost from both the long and short arm.

Tetrasomy 18p

An extra chromosome is present. This

chromosome is made up of two copies of the

short arm of chromosome 18.

Major conditions changes in chr-18

http://www.chromosome18.org/LinkClick.aspx?link=129&tabid=125http://www.chromosome18.org/LinkClick.aspx?link=129&tabid=125http://www.chromosome18.org/LinkClick.aspx?link=129&tabid=125http://www.chromosome18.org/LinkClick.aspx?link=129&tabid=125http://www.chromosome18.org/LinkClick.aspx?link=129&tabid=125

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Trisomy 18

There are three copies instead of the

usual two.

Major conditions changes in chr-18

http://www.chromosome18.org/LinkClick.aspx?link=130&tabid=125http://www.chromosome18.org/LinkClick.aspx?link=130&tabid=125http://www.chromosome18.org/LinkClick.aspx?link=130&tabid=125http://www.chromosome18.org/LinkClick.aspx?link=130&tabid=125

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Genes on chromosome 18

ATP8B1

CTDP1

FECH

LAMA3

LPIN2

NPC1

SMAD4

TCF4

TGIF1

TNFRSF11A

TTR

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Jenis-jenis kelainan terkait kromosom 18

congenital cataracts, facial dysmorphism, and neuropathy Fuchs endothelial dystrophy

hereditary hemorrhagic telangiectasia

junctional epidermolysis bullosa

juvenile polyposis syndrome

Majeed syndrome

Niemann-Pick disease

nonsyndromic holoprosencephaly

osteopetrosis

Paget disease of bone Pitt-Hopkins syndrome

porphyria

progressive familial intrahepatic cholestasis

Transthyretin amyloidosis

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JUVENILE POLYPOSIS SYNDROME

characterized by multiple noncancerous (benign) growthscalled juvenile polyps.

occur in the gastrointestinal tract, typically in the large

intestine (colon). typically develop polyps during the first two decades of life.

Polyps may cause:

gastrointestinal bleeding

a shortage of red blood cells (anemia) abdominal pain, and

Diarrhea

Changes in conditions of Chr-18

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Approximately 15 % of people with juvenile polyposis syndrome

other abnormalities

o a twisting of the intestines (intestinal malrotation),

o heart or brain abnormalities,

o an opening in the roof of the mouth (cleft palate),

o extra fingers or toes (polydactyly), and

o abnormalities of the genitalia or urinary tract.

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Mutations in the BMPR1A gene or the SMAD4

gene disrupt cell signaling and interfere with

their roles in regulating gene activity and cell

proliferation. This lack of regulation causes

cells to grow and divide in an uncontrolled

way, which can lead to polyp formation.

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Scheme of Juvenile Polyposis syndrome

BMPR1A gene --- SMAD4 genes

making proteins that are involved in transmitting chemicalsignals from the cell membrane to the nucleus.

regulate cell growth and division (proliferation) and the

activity of particular genes.

disrupt cell signaling and interfere with theirroles in regulating gene activity and cell

proliferation.

18q21.1

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Pitt-Hopkins Syndrome (PTHS)

caused by a mutation within or a completedeletion of the TCF4 gene.

instructions that tell the body how to growand develop.

The TCF4 gene is located on the long arm of

chromosome 18. Some individuals that have distal 18q- are

missing the TCF4 gene.

Changes in conditions of Chr-18

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Characteristics:

PTHS changes the way the brain develops andfunctions.

The eyes may be crossed (strabismus) or near-sightedness (myopia)

Scoliosis or flat feet

Cryptorchidism

chronic constipation

Facial Features