Chromosomes,located Genes on them and associated Diseases/Syndromes Part -1 ( Important topic for AIIMS/NEET/DNB)

Chromosome 1

Genes-

p-arm

COL 11A1  collagen protein

q-arm

PSEN2: presenilin 2 (Alzheimer disease 4)

HPC1: gene for prostate cancer

Diseases-

Alzheimer disease type 4

Ehlers-Danlos syndrome

Gaucher disease

Stickler syndrome-(hereditary progressive arthro-ophthalmopathy), Mutations in the COL11A1, COL11A2 and COL2A1 genes cause Stickler syndrome.

Chromosome 2

Genes-

k-kappa light chain gene

TPO: thyroid peroxidase

Type 3,4 & 5 collagen

PAX3: paired box gene 3 (Waardenburg syndrome 1)

Diseases-

Alport syndrome

Ehlers–Danlos syndrome, classical type

Chromosome 3

Genes-

p-arm

Collagen, type VII

VHL: von Hippel-Lindau tumor suppressor

q-arm

ZNF9: zinc finger protein 9 (a cellular retroviral nucleic acid binding protein)

ADIPOQ: adiponectin

Diseases-

Alkaptonuria

Dandy Walker Syndrome

Von Hippel-Lindau syndrome-mutations of the von Hippel–Lindau tumor suppressor (VHL) gene on the short arm of chromosome 3, The most common tumours found in VHL are central nervous system and retinal hemangioblastomas, clear cell renal carcinomas, pheochromocytomas, pancreatic neuroendocrine tumours, pancreatic cysts, endolymphatic sac tumors and epididymal papillary cystadenomas.

Chromosomes 4

Genes-

ANK2: ankyrin 2,

Complement Factor I: Complement Factor I

Chemokine (C-X-C motif) ligand

Huntingtin: huntingtin protein (Huntington’s disease)

PKD2: polycystic kidney disease 2 (autosomal dominant)

Factor XI: Mutations cause Haemophilia C

Multiple myeloma- balanced translocations t(4;14)

Diseases-

Achondroplasia

Facioscapulohumeral muscular dystrophy

Hemophilia C

Huntington’s disease

Hirschprung’s disease

Wolf-Hirschhorn syndrome is caused by the deletion of the distal short arm of chromosome 4

Chromosomes 5

Genes-

APC: adenomatosis polyposis coli

FGF: fibroblast growth factor 1&4

SNCAIP: synuclein, alpha interacting protein (synphilin)

Diseases-

Cri du Chat-deletion of the end of the short (p) arm of chromosome 5.

Familial adenomatous polyposis-deletion of the APC tumor suppressor gene on the long (q) arm of chromosome 5

Homocystinuria

Myelodysplastic Syndrome

Sotos Syndrome-(cerebral gigantism)

Treacher Collins syndrome

Parkinson’s disease

Chromosome 6

Genes-

HFE: Hemochromatosis

Major histocompatibility complex (MHC)

PKHD1: polycystic kidney and hepatic disease 1 (autosomal recessive)

PARK2: Parkinson disease (autosomal recessive, juvenile) 2, parkin

Disease-

Ankylosing spondylitis, HLA-B

collagenopathy, types II and XI

Coeliac disease HLA-DQA1 & DQB1

Ehlers-Danlos syndrome, classical, hypermobility, and Tenascin-X types

Hemochromatosis

Rheumatoid arthritis, HLA-DR

Systemic lupus erythematosus

Guillain Barre Syndrome

Diabetes mellitus type 1, HLA-DR, DQA1 & DQB1

Chromosome 7

Gene-

Cystic fibrosis CFTR gene

Diseases and syndromes-

CHARGE syndrome

cystic fibrosis

Osteogenesis imperfecta

Pendred syndrome

Williams syndrome-deletion of genetic material from a portion of the long (q) arm of chromos

Part-2 is coming soon……

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CONCEPT OF GENOMIC IMPRINTING AND DISEASES

We will try to understand concept of genomic imprinting by example of Prader Willi syndrome & Angelman syndrome.

Chromosome 15 q 11-13 have 2 sets of gene : PWS Region and AS gene.

A normal individual will have a pair of chromosome no 15 one from father and one from mother . PWS region of 15 q 11-13 is trancriptionally active only on the chromosome inherited from FATHER. These genes are transcriptionally inactive (imprinted) on the copy of chromosome 15 inherited from mother. SO THE PWS REGION ON CHROMOSOME SHOW MATERNAL IMPRINTING [ Kindly note that this process of gene silencing is called as imprinting and the transcriptionally inactive gene is said to be imprinted (ref : page 89 Medical Genetics elsevier 4thed)]

Also note that this process of imprinting in itself is not enough to cause a disease as PWS region is still functioning in a individual.

Then q arises how does PRADER WILLI SYNDROME occurs ??

PRADER WILLI will occur if PWS region gene are not present/functioning in a person.

So Prader Willi syndrome will occur if a gene deletion involving PWS region on chromosome15 is inherited from father. As only paternaly inherited PWS  gene is normally functional and maternal gene is already silent ( imprinted). So gene deletion on paternal ch 15 leads to absence of any functional copy of gene resulting in PRADER WILLI SYNDROME.

Other mechanism is that if a child inherits both copies of chromosome 15 from mother = UNIMATERNAL DISOMY , as in this situation also no functional copy of PWS gene is present.

So we get to conclusion that:

[1] PRADER WILL SYNDROME IS DUE TO

[a] INHERITENCE OF DELETION OF 15q11-13 FROM FATHER (70 % cases of PWS)*

[b] UNIMATERNAL DISOMY

[2] GENE RESPONSIBLE FOR PRADER WILLI SYNDROME ie PWS gene on 15q11-13 IS NORMALLY MATERNALLY IMPRINTED [ YES ITS TRUE 🙂 ]

by same explanation we will reach to conclusion that

[1] ANGELMAN SYNDROME IS DUE TO :

[a] INHERITENCE OF DELETION OF 15q11-13 FROM MOTHER

[b] UNIPATERNAL DISOMY

[2] GENE RESPONSIBLE FOR ANGELMAN SYNDROME ie AS GENE on 15q11-13 IS NORMALLY PATERNALY IMPRINTED [ YES ITS TRUE 🙂 ]

FEATURES OF BOTH SYNDROMES

[Q1] Not seen in Prader willi syndrome……
[A] short stature
[B] hypotonia
[C] obesity
[D] hypogonadism
[E] severe mental retardation

[Q2] which is not seen in Angelman syndrome…..
[A] seizure
[B] ataxic gait
[C] severe mental retardation
[D] hypogonadism

Ans :
[Q1] =Ans= [e] In prader willi mild to moderate mental retardation is seen and not severe one.

Moreover prader willi = short stature + hypotonia + small hands and feet + obesity + mild to moderate mental retardation + hypogonadism .

Note that severe mental retardation is a feature of Angelman syndrome.

[Q2]=Ans = [d]

NOTE ; EXAMPLE OF GENOMIC IMPRINTING
{1} PRADER_ WILLI ( 15q 11-13)
{2} ANGELMAN ( 15q 11-13)
{3} BECKWITH_WIEDMANN SYNDROME( 11p)
{4} RUSSELL_ SILVER SYNDROME (11p 15.5)