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Genetic Disorders 1

The document discusses genetic disorders and provides information on DNA, genes, inheritance patterns, types of genetic mutations, and examples of genetic disorders. It covers topics like single gene defects, cytogenetic abnormalities, multigenetic disorders, and inheritance patterns including autosomal dominant, autosomal recessive, and X-linked disorders.

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14 views

Genetic Disorders 1

The document discusses genetic disorders and provides information on DNA, genes, inheritance patterns, types of genetic mutations, and examples of genetic disorders. It covers topics like single gene defects, cytogenetic abnormalities, multigenetic disorders, and inheritance patterns including autosomal dominant, autosomal recessive, and X-linked disorders.

Uploaded by

Homed Opri
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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GENETIC DISORDERS

By:
Dr: Manhal AbdulGadir
MBBS U of K
MD clinical pathology U of K
OBJECTIVES
• By the end of this lecture students should be able to:
• Revise the normal human genetics and cell division
• Differentiate between mutations and cytogenetic
disorders
• Describe the Mendalian inheritance patterns and
examples of each
• Describe the types of mutations and cytogenetic
disorders
• Describe some of the common genetic disorders and
their clinical features
The DNA molecule
• Deoxyribonucleic
acid (DNA):
Located in the
nucleus, rapped up
in structures called
chromosomes

46 Chromosomes -23
Pairs in every cell
What is a gene?
• A part of the DNA
that codes for a
protein.

• Not all the DNA


codes for proteins.

• 20000 to 25000
genes in the human
genome.
Genome
☺ Sum total of all genes contained in a cell’s
chromosomes
☺ Identical in all cells
☺ Not all genes are expressed in all cells
☺ Not all genes are active all the time
☺ May code for enzymes or other functional
proteins, structural proteins, regulators of
other genes
DNA replication occurs during the
life of a cell = the Cell Cycle
• DNA replicates (makes a copy of itself) to
produce DS chromosomes
• During this time, the cytoplasmic contents
also duplicate
• Spindle tubules form to aid
in the process of cell division
– Mitosis in body cells
– Meiosis in sex cells
Definitions
- Locus: specific site of a gene on the chromosome.

- Alleles: alternate forms of a gene can occupy the


same locus

- Recessive gene: expressed only when homozygous

- Dominant gene: expressed when heterozygous

- Sex-linked gene: only X-linked in males


Genetic diseases
• Traditionally - 3 types of diseases
• 1. Genetically determined
• 2. Environmentally determined
• 3. BOTH.
• up to 20% of pediatric in-patients have genetic
abnormality
• about 50% of spontaneous abortuses have chromosomal
aberration
• only mutations that are not lethal are reservoir of genetic
diseases
• SINGLE GENE DEFECTS
✓At the level of genes
• CYTOGENETIC ABNORMALITIES
✓At the level of chromosomes
• MULTIGENIC DISORDERS
✓Gene polymorphism and environmental
factors
Mutations in Protein-Coding Genes
• Mutation refers to permanent changes in the
DNA.
1-Point mutations:
• Result from the substitution of a single nucleotide
base by a different base, resulting in the replacement
of one amino acid by another in the protein product.
• Mutation in the β-globin chain of hemoglobin giving
rise to sickle cell anemia is an excellent example of a
point mutation.
2-Frameshift mutations :
Occur when the insertion or deletion of one or two base
pairs alters the reading frame of the DNA strand.
3-Trinucleotide repeat mutations:
Amplification of a sequence of three
nucleotides. Eg: Fragile X syndrome (mental
retardation)
Epigenetic Changes
• Epigenetic changes are those involving modulation of
gene or protein expression in the absence of
alterations in DNA sequence (i.e., mutation) or
structure of the encoding gene.
1- Alterations in the methylation
2- Histone modifications
3- Post translation modifications.
Disorders of Autosomal Dominant
Inheritance
• Disorders of autosomal dominant inheritance
are manifested in the heterozygous state, so at
least one parent in an index case usually is
affected; both males and females are affected,
and both can transmit the condition
• Some patients do not have affected parents.
Such patients owe their disorder to new
mutations involving either the egg or the
sperm from which they were derived.
• In many conditions, the age at onset is
delayed, and symptoms and signs do not
appear until adulthood (as in Huntington
disease).
Eg: Autosomal Dominant Disorders
• Familial hypercholesterolemia.
• Polycystic kidney disease.
• Hereditary spherocytosis.
• Marfan syndrome.
• Huntington disease.
Disorders of Autosomal Recessive
Inheritance
• They occur when both of the alleles at a given
gene locus are mutants; therefore, such
disorders the siblings have one chance in four
of being affected (i.e., the recurrence risk is
25% for each birth).
• Onset is frequently early in life.
Eg :Autosomal Recessive Disorers

• Cystic fibrosis
• Phenylketonuria (Phenylalanine hydroxylase Enzyme)
• Tay-Sachs disease (Hexosaminidase Enzyme)
• Severe combined immunodeficiency( Adenosine
deaminase Enzyme)
• α- and β-Thalassemias
• Sickle cell anemia
X-Linked Disorders
• All sex-linked disorders are X-linked. No Y-linked
diseases are known as yet.
• Most X-linked disorders are X-linked recessive and
are characterized by the following:
-They are transmitted by heterozygous female
carriers only to sons, who of course are
hemizygous for the X chromosome.
- Heterozygous females rarely express the full
phenotypic change, because they have the paired
normal allele
• An affected male does not transmit the
disorder to sons, but all daughters are carriers.
Sons of heterozygous women have one chance
in two of receiving the mutant gene.
Eg:X-linked Recessive Inheritance

-Hemophilia A Factor VIII Coagulation


-Duchenne/Becker muscular dystrophy
Dystrophin: Structural protein
-Fragile X syndrome
Diseases Caused by Mutations in Genes
Encoding Structural Proteins
Marfan Syndrome:
• A connective tissue disorder of autosomal dominant
inheritance.
• Mutation affecting fibrillin, secreted by fibroblasts, is
the major component of microfibrils found in the
extracellular matrix.
• Skeletal abnormalities, ocular change is bilateral
dislocation, or subluxation, of the lens secondary to
weakness of its suspensory ligaments
• Cardiovascular system: mitral valve prolapse
Ehlers-Danlos Syndromes
• Are a group of diseases characterized by
defects in collagen synthesis or structure.
• The mode of inheritance encompasses both
autosomal dominant and recessive patterns.
• Because the abnormal collagen fibers lack
adequate tensile strength, the skin is
hyperextensible and joints are hypermobile.

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