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SINGLE GENE DISORDER
Learning Objectives
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Define pedigree
Identify symbols required to make pedigree
Define single gene disorders
Enlist different types of single gene disorders
Describe genetic changes which occur in these disorders
Enlist characteristics of single gene which gives variation in expression
of diseases
Pedigree
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Family tree
First person identified
– Index case proband, propositus or proposita
Definition
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The single gene is responsible for the disorder 
Mendelian pattern of inheritance
Over 10,000  identified
-2 % of general population
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Huntington Disease
Myotonic dystrophy
Hereditary motor and sensory neuropathy
Neurofibromatosis
Marfan syndrome
Cystic fibrosis
Inherited cardiac arrhythmias and cardiomyopathies
Spinal muscular atrophy
Duchenne muscular dystrophy
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Hemophilia
Huntington Disease
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1872 Dr.George Huntington
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Genetics  AD, penetrance, low mutation rate, anticipation
markers
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located at 5’ region
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Expansion of CAG
Normal alleles  26 or few CAG repeats
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new mutation
-39 CAG late onset or complete
absence of disease expression (non penetrance)
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Myotonic Dystrophy
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Common MD
1 in 8000
Slow progressive weakness and myotonia, cardiac conduction defects,
cataract
Genetics 
consists of 37 repeats.
Marfan Syndrome
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Beal syndrome, congenital contractual arachnodactyly
AD Fibrous connective tissue type 1 fibrillin glycoprotein  FBN1
gene
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Cystic Fibrosis
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Mucoviscidosis
AR 1 in 2000 – 1 in 3000
Chronic lung disease, pancreatic function is impaired
CFTR
exons
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Mutation 
F 508 (70%)
Over 1300 mutations (missences, framshift, splice site, nonsence &
deletion) .
Duchenne Muscular Dystrophy
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BMD 1 in 3500 males
DMD 1 in 20,000 males
Usually  slow progressively muscle weakness
Genetics  X linked recessive inheritance
Dystrophin gene
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and promoter mutations
Hemophilia
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Inherited coagulation disorder
1 in 5000 males 
activation of prothrombin to thrombin
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186 kb with 26 exons 9kb mRNA transcrip
nonsense and missence mutation
Factor IX gene  34 kb with 8 exons
Variable Expression
Expressivity is a term used in genetics to refer to variations in a
phenotype among individuals carrying a particular genotype
Variable expressivity occurs when a phenotype is expressed to a
different degree among individuals with the same genotype.
Example:
Hemochromatosis
Incomplete Penetrance
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Penetrance: The frequency with which a heritable trait is manifested by
individuals carrying the principal gene or genes conditioning it.
when penetrance is less than 100%. incomplete penetrance
Example: Familial cancer, retinoblastoma
Pleiotrophy
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Pleiotropy occurs when one gene influences multiple phenotypic traits.
Consequently, a mutation in a pleiotropic gene may have an effect on
some or all traits simultaneously
Example : Marfan Syndrome.
Locus hetrozygosity
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It exists when the same disease phenotype can be caused by mutation
in different loci
It is especially important when genetic testing is performed by testing for
mutation at specific loci.
Example: Osteogenesis imperfecta type 2
Anticipation
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Its a phenomenon whereby the symptoms of a genetic disorder become
apparent at an earlier age as it is passed on to the next generation.
In most cases, an increase of severity of symptoms is also noted.
Anticipation is common in trinucleotide repeat disorders such as
Huntington's disease and myotonic dystrophy where a dynamic
mutation in DNA occurs.
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Imprinting
A small no. of genes are transcriptionally active only when transmitted
by one of the two parents
Example: Prader-Willi Syndrome
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Referance
Kaplan Biochemistry and Medical Genetics
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