Clinical genetics

★ Topics to read from Davidson

- Cell division, differentiation, migration topic
- Cell death, apoptosis, senescence
- Neuclotide substitution subclass (reading)
- Autosomal dominant inheritance : Character and example ( most important topic)
- Autosomal recessive inheritance : Character and example ( most important topic)
- X linked inheritance : Character and example ( most important topic)
- Mitochondrial inheritance : Character and example
- Gene therapy ( conditions treated with gene therapy)
- Induced pluripotent stem cells and regenerative medicine ( Reading)

★ Boxes to read
3.1 (name and definition),
3.2 ( name only, coding and non coding আলাদা করে জানতে হবে),
3.3 (name only),
3.5 ( inheritance pattern, clinical presentation, disease mechanism),
3.6 ( inheritance pattern, clinical presentation, disease mechanism),
3.7 ( name of Mitochondrial diseases), 3.8( name of imprinting disorder),
3.9( reading),
3.11 ( syndrome name)

★ মেইনলি ডেভিডসন পড়বেন। সাথে যেকোন গাইড/ নোট/ শিট দেখবেন। যেকোনটা। জেনেসিসের জেনেটিক্স শিট টা
ভাল। আর আমার ভাল লেগেছে MRCP Basic Science এর জেনেটিক্স অংশটা।
★আর যদি এমন হয় যে শুধু একটা টপিক পড়ার সময় আছে, তাহলে AD, AR, XR এর character and
example পড়ে চলে যাবেন। প্রশ্ন পাবেন, কনফার্ম।

***Genetics
[Link] & Examples of Mendelian Disorders
[Link] Classic Inheritance - Examples & Examples of Imprinting Disorders
[Link],Turner,Klinfilters-Details
[Link] Inheritance - Characteristics & Examples

#Genetics Tips

🕸️ Genetics: The study (science) of heredity and the variation of inherited

characteristics.
🕸️ Heredity / Inheritance: Process of transmission of character (the passing on of
physical or mental characteristics) genetically from one generation to another
(next generation).

⚡Genetic Code, Triplet = Located in DNA

⚡Codons = are Located in mRNA
⚡Start codon (Initiation code) = AUG for Methionine(Amino acid)
⚡Stop codon = 3 in number. UAA UAG UGA
⚡Anti codon = are Located in tRNA

✩ Genome = the complete set of Chromosomes (genes or genetic material) present in a

cell or organism.
The human genome contains over 20,000 genes, although many of these are inactive or
silenced in different cell types, reflecting the variable gene expression
responsible for cell-specific characteristics.

The packaging of genes:

✧ DNA
✧ Chromatin
✧ Chromosomes

✻ A nucleosome is the basic structural unit of DNA packaging in eukaryotes.

✻ Gene: Basic unit of inheritance by which characteristics are passed from one
generation to another (next generation).
💍 Gene is the part of the DNA where genetic information is stored.

✻ Genes are functional units encoded in double-stranded deoxyribonucleic acid

(DNA), packaged as chromosomes and located in the nucleus of the cell.
The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence
of nucleotides in DNA that is transcribed to produce a functional RNA.
There are two types of molecular genes: protein-coding genes and noncoding genes.

⍟ Locus: Location (Site) of gene on chromosome

⍟ Allele: Alternative forms of a gene occupyong the same locus on a particular
chromosome.
Each of two or more Alternative forms of a gene that arise by mutation
and are found at the same place on a chromosome is called allele.

Karyotype
A karyotype is a photographic representation of a stained metaphase spread in which
the chromosomes are arranged in order of decreasing length.

The genetic code (Language) is a set of three-letter combinations of nucleotides

called codons(Word), each of which corresponds to a specific amino acid or stop
signal.
There are 64 different codons with some redundancy in the system: 61 codons encode
one of the 20 amino acids,
and the remaining three codons – UAA, UAG and UGA (known as stop codons) – cause
termination of the growing polypeptide chain.

Properties of genetic code:

• Genetic code is a triple code (Triplet).
• Unambiguous/Specificity (Genetic code is same for all living organism → Same code
for same amino acids in all organisms)
• Universality
• Redundancy/Degenarate
• Non overlapping
• Commaless
• Any change in the arrangement of bases of codon, lead to defective protein.

Congenital anomalies are structural defects that are present at birth, although
some, such as cardiac defects and renal anomalies, may not become clinically
apparent until years later.
As will be evident from the ensuing discussion, the term congenital does not imply
or exclude a genetic basis.

✭ Chromosomes
✧ Short arm = p arm
✧ Long arm = q arm
 ✧ Telomere = Terminal part = (A telomere is a region of repetitive DNA
sequences at the end of a chromosome.)
✧ Centromere = Constricted point of the chromosomes (Centromeres can be
defined as the compressed region or a part of elongated chromosomes.)

The main difference between chromatin and chromosome is that

chromatin consists of the unravelled condensed structure of DNA for the purpose of
packaging into the nucleus
whereas chromosome consists of the highest condensed structure of the DNA
doublehelix for the proper separation of the genetic material.

😊 Chromatin is basically a DNA in the nucleus which is the uncondensed form of

chromosomes. When a DNA replicates itself, it produces two chromatids which are
joined together at centromere. Both chromatids are genetically identical.
😊 When the cell is not dividing, the strands of DNA are called as chromatin and in
mitosis after replication, the chromosomes have two chromatids.
😊 Chromatin is the indistinguishable mass of DNA molecules whereas chromatids are
a part of chromosome attached to it with a centromere.

A single copy of the human genome comprises approximately 3.1 billion base pairs of
DNA, wound around proteins called histones.
The unit consisting of 147 base pairs wrapped around four different histone
proteins is called the nucleosome.
The structure of a nucleosome consists of a segment of DNA wound around eight
histone proteins (4 pairs) and resembles thread wrapped around a spool.
Sequences of nucleosomes (resembling a string of beads) are wound and packaged to
form chromatin.

Chromatin
Heterochromatin = tightly wound, densely packed (Supercoiled) chromatin is called
heterochromatin (dense, inactive = No genetic material, transcription cannot occur)
Euchromatin = open, less tightly wound chromatin is called euchromatin. (disperse,
active = Contains genetic material, transcription can occur)

★★★★Multifactorial (polygenic) inheritance disorders★★★★

Multifactorial or polygenic disorders

Complex multigenic disorders—so-called “multifactorial or polygenic disorders”—are
caused by interactions between genetic variants and environmental factors.

♦️Cleft lip with or without cleft palate

♦️Neural tube defects (anencephaly, spina bifida)
♦️Congenital dislocation of the hip
♦️Congenital heart defects
♦️Gout
♦️Pyloric stenosis
♦️Talipes(Club foot)
♦️Diabetes
♦️Hypertension (high blood pressure)
♦️Asthma
♦️Alzheimer's disease
♦️Epilepsy
♦️Schizophrenia
♦️Obesity
♦️Parkinson's disease

💢 Autosomal Disease → Both Male & Female are equally affected.

💢 Dominant Disease → No Carrier State
💢 X-linked Disease → No Male to Male Transmission

Autosomal dominant disorder: Features :

♦️
At least one parent of a case is affected.
♦️
Both male and female can be equally affected
♦️
Both male and female can transmit disease
♦️
Heterozygotes state
♦️
No carrier condition
♦️
Half of offspring are affected
♦️
Unaffected individual cannot transmit disease
♦️
Father-son transmission may be observed
♦️
Variable expression reduced penetrance/incomplete penetrance
♦️
Can exhibit anticipation
♦️
High new mutation rate
♦️
Vertical transmission occur
♦️
Less severe than autosomal recessive.
♦️
Usually associated with structural abnormalities

Autosomal recessive disorder Features :

💥Both sexes are equally affected
💥Homozygous state
💥Parents are usually unaffected, healthy carriers
💥If both parents are carriers....
⬆ ️25% of offspring are homozygous and affected
⬆️25% of offspring are genetically normal
⬆️50% of offspring are carriers
💥If one parent carriers the gene:
⬆️50% of offspring are normal
⬆️50% of offspring are carriers
💥Onset is often early in life, high mortality rate, usually only one generation is
affected.
💥Complete penetrance is common
💥Expression of defect tends to be more uniform
💥Horizontal transmission occur
💥Variable expressivity is less than autosomal dominant inheritance
💥Usually associated with metabolic abnormalities
🎲X- linked Dominant :
➡ ️FAIR COX
F- Fragile X syndrome
A -Alport syndrome
I-Incontinentia pigmentis
R- Rett syndrome
C- Child syndrome, Coffin syndrome
O- Of D1 gene disease
X- X linked Dominant

🎲X- linked recessive :

➡️A Oblivious Female Will give her boys her X linked disease (very bad girl)
A-Alport syndrome ( its may be AR)
Oblivious - Ocular albinism
Female - Fabry's disease
Will- wiskoot aldrich syndrome
Give - G6PD ⬇ ️
Her- Hemophilia A & B
Boys - Brutton Agamaglobinaemia
Linked - Lesch Nyhan syndrome
Disease - DI, Duchene muscular dystrophy

★★★Indication of gene therapy★★★

DCH is PAST:
💥D-Duchenne muscular dystrophy
💥C-Cystic fibrosis, cancer
💥H-Haemophilia A, familial hypercholesterolaemia
💥P-Phenylketonuria
💥A-Adenosine deaminase deficiency, alpha-1 antitrypsin deficiency
💥S-Sickle cell disease
💥T-Thalassaemia

Indication of chromosome analysis:

★ Congenital Malformation
★ Mental retardation
★ Repeated abortion
★ Sex determination
★ Paternal diagnosis

Telomere:
★ Ends of chromosome is made of special DNA
★ Essential structures
★ Provides structural stability by sealing both ends
★ Protects both ends from damage.
★ Do not contain the codes for proteins & So, they are not genes.

Autosomal dominant inherited cancer:

♦️
Retinoblastoma
♦️
Melanoma
♦️
Familial adenomatous polyposis (FAP)
♦️
Hereditary non-polyposis colon cancer (HNPCC).
♦️
Neurofibromatosis 1 and 2
♦️
MEN-1,MEN-2

Recurrent deletions, microdeletiins and contagious gene defects :

William smith PAD পড়ে খেলতো।
⚡William's syndrome
⚡Smith-Magenis syndrome
⚡Prader-Willi syndrome
⚡Angelman's syndrome
⚡Di-George syndrome

[Link]+ choreoathetosis+ mental retardation + x linked recessive. Dx?

A. Lesch Nyhan syndrome

Q. Becker muscular dystrophy caused by mutation in which gene?

A. Dystrophin

Q. DMD duchenne muscular dystrophy (X-linked recessive)caused by mutation in which

gene?
A. Dystrophin (Mutations or deletions encompassing/within the DMD (dystrophin)
gene located at Xp21)

Q. Mutation in which location responsible for Duchene muscular dystrophy ?

A. gene located at Xp21

• DMD encodes dystrophin, a major structural component of muscle

• Dystrophin links the internal cytoskeleton to the extracellular matrix

Disease variants
• Becker muscular dystrophy, although a separate disease, is also
caused by mutations in the dystrophin gene
• In Duchenne muscular dystrophy, there is no dystrophin protein,
whereas in Becker muscular dystrophy there is a reduction in the amount or
alteration in the size of the dystrophin protein

Q. Which disease affects almost all boys with Duchenne muscular dystrophy?
A. Cardiomyopathy DCM

Q. Mitochondrial DNA is transmitted by which one?

A. Oocytes
Q. Which is the principal pathological abnormality of klinefelter Syndrome?
A. Dysgenesis of seminiferous tubules

Q. Genetic anticipation present?

A. Autosomal Dominant

Genetic anticipation: A phenomenon in which the signs and symptoms of some genetic
conditions tend to become more severe and/or appear at an earlier age as the
disorder is passed from one generation to the next.
Anticipation occurs only in Autosomal Dominant Disorder.

Q. Which disease is associated with genetic anticipation?

A. Anticipation is common in trinucleotide repeat disorders, such as Huntington's
disease and myotonic dystrophy, where a dynamic mutation in DNA occurs.

Q. X linked inherited ataxia ?

A. Adrenoleukodystrophy

Q. A 30 year old male presents has intermittent jaundice and anaemia.

He is diagnosed with glucose 6 phosphate dehydrogenase (G6PD) deficiency.(XR)
His wife has normal G6PD activity.
What is the likelihood of their children developing the condition phenotypically?

A. All their children will be affected

B. All their sons will be affected
C. All their daughters will be affected
D. 50% of their daughters will be affected
E. None of their children will be affected

Answer: E. None of their children will be affected.

Because X-linked Recessive Disorder No Male to Male Transmission.
So, All sons are healthy (Normal) & All daughters will be Carrier.

Pearls of genetics
⚡Small penis+small testes---> Klinefelter syndrome
⚡Large testes+Large mouth--> Fragile-X syndrome
⚡Microophthalmia+polydactyly--->Pattau syndrome
⚡Micrognathia(small mouth)+Rocker bottom feet--> Edward syndrome
⚡Delayed puberty +Anosmia+ undescended testes--> kallmann Syndrome.
✔ ️ Contiguous gene defect :
💥Di George syndrome
💥Prader willi syndrome
💥Angleman's syndrome
💥Williams syndrome
💥Smith magenis syndrome

♣️
♣️DiGorge syndrome / Velocardiofacial syndrome :
🐈 CAT 22
কারন কি? 22q11 gene deletion হওয়ার জন্য 3/4 pharyngeal pouch development না হওয়ার
জন্য।
➡️3rd pharyngeal pouch থেকে Thymus development করে।
➡️ 3rd pharyngeal pouch থেকে Inferior parathyroid gland development করে।
➡️4th pharyngeal pouch থেকে superior parathyroid gland development করে।
💥এখন Thymus এর কাজ হচ্ছে T-lymphocyte maturation করা। যেহেতু এখানে Absent আছে Thymic
development সুতরাং Very low circulating T cells পাওয়া যাবে। ( Normal development of
bone marrow)
💥 The parathyroid glands (light pink) produce parathyroid hormone, which increases
levels of calcium in the blood.সুতরাং parathyroid gland development না হলে
Hypocalcemia হবে।
🐈🐈CAT 22 এর
C- Congenital Heart disease, cleft lip and clefts plate
A- Abnormal face
T- Tracheo-oesophageal fistula, Thymic aplasia.
22 - 22q11 gene deletion

#Genetics
💢💢💢 VVI 💢💢💢
Chromosome 15 এর সাথে ৩ টি গুরুত্বপূর্ণ Syndrome আছে। ৩ টি syndrome পরীক্ষায় আসার মতো।
Syndrome ৩ টি হচ্ছে - "MAP"
M- Marfan syndrome.
A- Angleman's syndrome.
P- Prader willi syndrome.
1🎲 Marfan syndrome : Chromosome 15 এর Fibrilin gene mutation হয়ে হয়। অন্য দুটি থেকে
আলাদা কারন বাকি দুটিতে mutation + deletion হয় Gene এর Allele ( wait সব বুঝবেন).. প্রধানত
কি কি Features থাকবে pt এর --
1) Long arms, legs, finger and toes.
2) Overflexed joint & soliosis.
3) Mitral valve prolapse.
2🎲 Angleman's syndrome : হাসতে দেখো, গাইতে দেখো না ( No)..... দেখো না কেউ আমার মনের(
হৃদয়ের) যন্ত্রনা।
★হাসতে দেখো - Happy puppet syndrome ও বলা হয় কারন দেখতে মনে হয় রোগী হাসছে সবসময়।
★ গাইতে দেখোনা ( না) - Absent speech তাই learning disability..
★ মনের (হৃদয়ের) যন্ত্রনা - তবে ECG abnormality না, EEG হবে। 😄😄
কারন কি? Chromosome 15 এর UBE3A gene এর Maternal allele এর Imprinted region
deletion হয়।
🎲 Prader-will syndrome : যাই পাই -তাই খাই ( Hyperphagia) .. Marfan এ হাত পা অনেক
লম্বা লম্বা কিন্তু এখানে small hands & feet( উল্টো)
কারন- Chromosome 15 এর Nectin gene এর paternal allele এর Imprinted region deletion
হয়( 3p - Prader, paternal allele delete & phagia besi 😆)
( chromosome এর যে জায়গায় জিন পাওয়া যায় তাই লোকাস। অর্থাৎ জিনের বাড়ি। প্রতি বাড়িতে স্বামী
স্ত্রী থাকবে। এখানে স্বামীকে বলি paternal allele আর স্ত্রীকে Maternal allele...লোকাসে
বসবাসকারী Allele নিয়েই জিন। তার মানে এই না যে স্বামী স্ত্রী ছাড়া আর কেউ বাড়িতে থাকে না। এজন্য
সব সময় লোকাসে ২ টি জিন পাবেন এমন না, বেশিও থাকতে পারে। তবে ২ টি থাকাই স্বাভাবিক)

Q. Which enzymes called terminal transferase??

A. Tolemerase

[Link] neural deafness, Visual abnormity & haematuria. Culprit of gene? Dx =

Alport syndrome
A.COL4A5

Q. Repair of DNA in which stage of Cell division?

A. Mitosis--G2 Phase

Q. Centriole move to the opposite end in which phase of mitosis?

A. Prophase
Prophase> Centrioles move to opposite end
Metaphase> Centrioles complete their migration to opposite end

[Link] replication in which stage of Cell division?

A. S -Phase

Q. ORF (Open Reading Frame) in humans most commonly starts with which Amino acid?
A. Methionine

Q. 47,XY,+13, Cleft lip & palate+Polydactyly+frequent congenital heart disease.

Which disease?
A. Patau syndrome Remember all "P"

Q. Down's syndrome + feature of malabsorption. Dx?

A. Coeliac disease

Q.A 17 year old girl presents with primary amenorrhoea.

On examination,she has a high arched palate, immature external genitalia and
absence of breast development.
Her height is 151cm (2nd centile for age and gender)
What is the most likely dx?

[Link]
[Link] syndrome
[Link] dysgenesis
[Link]'s syndrome
[Link] androgen insensitivity

Answer: [Link]'s syndrome

Q. Hyperphagia present in which genetic disease?

A. Prader willi syndrome

Q. 47,XY,+18 +characteristic skull & facies+Malformation of heart & kidney. Which

disease?
A. Edward

Q. Which enzyme mutation occurs in Werner's syndrome?

A. DNA helicase

Q. Alpha-1 Antitrypsin Deficiency is encoded by which gene?

A. SERPINA 1

Q. Robertsonian translocation occurs chromosome between?

A. 14,21 Robertsonian translocation in Down syndrome

[Link] sleep abnormalities present in which genetic disease?

A. Smith-Magenis Syndrome রাইতের বেলা sms বেশি চালাচালি হয় এইজন্য ঘুমের বারটা বাজে

[Link] one of the following is successful used in treatment of cutaneous T-cell

lymphoma?
a) Transtuzumab
b)Imatinib.
c) Vorinostat.
d)Bevacizumab
e) Bicalutamide.

Answer: c) Vorinostat (histone deacetylase inhibitor)

Q. Significantly Refuced life expectancy in

a)Down
b)Edward
c)Patau
d)Klinefelters
e)Turner

Answer: a)Down Syndrome

🧬🧬🧬🧬🧬🧬
🔰🔰🔰Increased Maternal ♀️age Is Related to ⛔⛔DOWN"S SYNDROME⛔⛔
🔰🔰🔰Increased Paternal ♂️age Is Related to ⛔⛔ACHONDROPLASIA⛔⛔
🧬🧬🧬🧬🧬🧬

Q. Mention some condition where female can be effected/ sufferer in X linked

recessive disease????
A. ⍟ Turner syndrome
⍟Lion hypothesisis

Q. In a neucleosome, how many base pairs wrapped around four different types of
histones?
A. 147

Q. Most important human disease caused by somatic mutations?

A. Cancer

Q. Cardiac outflow defect+clef palate found in which disease????

A. Di Geroge Syndrome

Cleft palate " found in

Di George/velocardiofacial syndrome 22q11.2
Patau’s syndrome (trisomy 13)

William's syndrome
-------------------
Supra-valvular aortic stenosis + Infantile hypercalcemia + learning disability

💢💢 Genetics disease & most common cardiac condition ( VVI for Part 1 SBA)
🦚Most common Cardiac anomaly in Rubella syndorme is PDA.
🦚Most common cardiac anomaly in Marfan syndrome is Aortic aneurysm.
🦚Most common cardiac Anomaly in Turner syndrome is Bicuspid aortic valve.
🦚Most common cardiac anomaly in Down syndrome is Endocardial cushion defect.
🦚Most common cardiac anomaly in IDM is Hypertrophic Cardiomyopathy(Obstructive).
🦚Most common cardiac anomaly in Edward syndrome is VSD.
❤️‍🔥 Most Common cardiac anomaly in Down syndrome --Endocardial Cushion defect
❤️‍🔥 Most common cardiac anomaly in Turner syndrome -- Bicuspid aortic valve
❤️‍🔥 Most common cardiac anomaly In marfan Syndrome---Aortic root dilatation then
mitral valve prolapse.
❤️‍🔥 Most common cardiac anomaly in Edward syndrome --Ventricular septal defect.

⚡Most common cardiac anomaly in marfan Syndrome → Aortic root dilatation then
mitral valve prolapse.
⚡Most common cardiac anomaly in Turner syndrome → Bicuspid aortic valve
⚡Most Common cardiac anomaly in Down syndrome → Endocardial Cushion defect
⚡Most common cardiac anomaly in Edward syndrome → Ventricular septal defect.

Nucleotide substitutions
The substitution of one nucleotide for another is the most common type of genomic
variation.
This is caused by misincorporation of a nucleotide during DNA synthesis or by
chemical modification of the base.
When these substitutions occur within ORFs of a protein-coding gene, they are
further classified into:
⌛ Synonymous or Silent – resulting in a change in the codon without altering the
amino acid
Synonymous or Silent → no amino acid change.
⌛ Non-synonymous (also known as a missense variant) – resulting in a change in the
codon and the encoded amino acid.
Non-synonymous or missense mutation → amino acid change Example - Sickle Cell
Anaemia (Sickle cell anemia results from the single amino acid substitution of
valine for glutamic acid in the beta-chain owing to a nucleotide defect that causes
the production of abnormal beta-chains in hemoglobin S.)
⌛ Stop gain (or nonsense variant) – introducing a premature stop codon and
resulting in truncation of the protein.
Stop gain or nonsense mutation → Nonsense variant causing premature
termination codon Example - Beta-Thalassemia
⌛ Splicing – disruption of normal splicing and therefore most frequently occurring
at the junctions between an intron and an exon.

Q. X-linked disease like( Becker & Duchenne) mostly associated with Which
Cardiomyopathy?
A. Dilated cardiomyopathy DCM

Pleiotropy: In genetics, Pleiotropy is defined as the expression of multiple traits

by a single gene.
Mutation of a single gene but widespred effect. e.g. Marfan's Sundrome.

Classification of Genetic Diseases or Disorders

Categories: First three are major categories.
1. Mendelian disorders.(Monogenic)
• These disorders follow the classic mendelian patterns of inheritance due to
mutation in single genes of large effects.
• Single-gene defects (mutations) follow the well-known mendelian patterns of
inheritance. g mendelian disorders:
• Mutations involving single genes follow one of three patterns of
inheritance:
✧ Autosomal dominant (AD),
✧ Autosomal recessive (AR),
✧ or X-linked (XR or XD).

2. Multifactorial disorders.
• These disorders are influenced by both genetic and environmental factors.
• The genetic component involves the additive results of multiple genes of
small effect.

3. Cytogenetic disorders or Chromosomal abnormalities.

• Numeric Abnormalities
• Structural Abnormalities

✯ Cytogenetic Disorders Involving Autosomes

✢ Down Syndrome (Trisomy 21) 47,XY,+21 or 47,XX+21

✢ Edwards Syndrome (Trisomy 18) 47,XY,+18 or 47,XX,+18
✢ Patau Syndrome (Trisomy 13) 47,XY,+13 or 47, XX,+13
✢ Cri du chat syndrome (deletion syndrome) which results from partial
deletion of the short arm of chromosome 5.
✢ DiGeorge syndrome or /velocardiofacial syndrome (22q11.2 deletion syndrome)
✢ Prader–Willi syndrome 15q11–q13 (deletions on paternal allele)
✢ Angelman syndrome 15q11–q13 (deletions on maternal allele encompassing
UBE3A)

✯ Cytogenetic Disorders Involving Sex Chromosomes

✢ Klinefelter Syndrome 47,XXY

✢ Turner syndrome 45,X
✢ Triple X syndrome 47,XXX
✢ XYY 47,XYY

4. Single-gene disorders with nonclassic inheritance (Atypical Patterns of

Inheritance).
• These groups of diseases resulting from mutations affecting single genes do not
follow the mendelian rules of inheritance:
✧ Diseases caused by triplet repeat mutations
✧ Diseases caused by mutations in mitochondrial genes
✧ Diseases associated with alteration of imprinted regions of the genome
✧ Disorders associated with gonadal mosaicism

Diseases associated with triplet and other repeat expansions

❖ Coding repeat expansion

☯ Huntington’s disease
☯ Spinocerebellar ataxia (type 1)
☯ Spinocerebellar ataxia (types 2, 3, 6, 7)
☯ Dentatorubral-pallidoluysian atrophy
☯ Machado–Joseph disease
☯ Spinobulbar muscular atrophy
❖ Non-coding repeat expansion (My Fragile Friend Friedreich = Non-coding)
☯ Myotonic dystrophy
☯ Friedreich’s ataxia
☯ Progressive myoclonic epilepsy
☯ Fragile X mental retardation
☯ Fragile site mental retardation 2 (FRAXE)

Triplet & Other repeat sequences থেকে বার বার যে সকল প্রশ্ন আসে এই গুলো খাতায় লিখে দিলাম।
সাথে মনে রাখবার একটি ফরমুলা।
Friedreich 👨‍🎤 GAA(n) গান গায়
Myo CTG( চিটাগং) যায় 🚌🚉
FraGile x এ GG (CGG) বেশি।
🐐 CAG'ol ( ছাগল) Huntington করি।

Q. Example of coding repeat expansion?

A. Hemophilia A
B. Huntington's disease ✅
C. Fragile X syndrome
D. Friedreich's ataxia
E. Myotonic dystrophy
Answer: B. Huntington's disease

[Link] repeat expansion disorders-

a) Huntington's disease ✅
b) Osteogenesis imperfecta ❌
c) Fragile x syndrome ✅
d) Alport syndrome ❌
e) Myotonic dystrophy ✅

TFTFT

Diseases Caused by Mutations in Mitochondrial Genes

Inheritance of mitochondrial DNA differs from that of nuclear DNA in that the
former is associated with maternal inheritance.
Diseases caused by mutations in mitochondrial genes are rare.
Leber hereditary optic neuropathy is the prototypical disorder in this group. This
neurodegenerative disease manifests as progressive bilateral loss of central vision
that leads in due course to blindness.

Genomic Imprinting disorders

Imprinting involves transcriptional silencing of the paternal or maternal copies of
certain genes during gametogenesis.
For such genes only one functional copy exists in the individual. Loss of the
functional allele (not imprinted) by deletions gives rise to diseases.

✧ Beckwith–Wiedemann syndrome
✧ Prader–Willi syndrome
✧ Angelman syndrome (AS)
✧ Pseudohypoparathyroidism
Multifactorial or polygenic disorders
Complex multigenic disorders—so-called “multifactorial or polygenic disorders”—are
caused by interactions between genetic variants and environmental factors.

♦️Cleft lip with or without cleft palate

♦️Neural tube defects (anencephaly, spina bifida)
♦️Congenital dislocation of the hip
♦️Congenital heart defects
♦️Gout
♦️Pyloric stenosis
♦️Talipes(Club foot)
♦️Diabetes
♦️Hypertension (high blood pressure)
♦️Asthma
♦️Alzheimer's disease
♦️Epilepsy
♦️Schizophrenia
♦️Obesity
♦️Cerebral Palsy (CP)

☢ Genetic disorder associated with mental retardation:

***PoWAR of DHF.... Mental retardation
Po= Phenylketonuria
W= William's disease
A= Angelman syndrome
R= RETT syndrome (Rett syndrome is a rare genetic neurological and developmental
disorder that affects the way the brain develops)
of= ×
D= Down's syndrome, Duchenne muscular dystrophy
H= Homocysteinurea, Huntington's disease
F= Fragile X syndrome

Causes of Tall stature :

-Constitutional (most common)
-Gigantism
-Klinefelter syndrome
-kallmann syndrome
-Marfan syndrome
-Homocystinuria