بسم الله الرحمن الرحيم. Single Gene Disorders. Dr. Nasser Elhawary. Prof. of Medical Genetics. Definitions …. Human Genetics : is the science of biological variations in humans. Medical Genetics : is the science of human biologic variations as it relates to health and disease .
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
Dr. Nasser Elhawary
Prof. of Medical Genetics
1- Dominant 2- Recessive
(arise from meiotic non-disjunction in the father)
Frontal (a) and lateral (b) appearance of a patient with DS
Typical Down’s syndrome foot
Typical Down’s syndrome hand
Trisomy 21 FISH karyotype
GTG-banding of a trisomy 21 patient
- 1ry Amenorrhea & Infertility associated with:
- short stature (< 5 feet)
- webbing of the neck
- increased carrying angle at elbow
- cardiovascular abnormality.
- renal abnormality.
Barr body: A condensed, inactivated X chromosome present in most female
mammals in all somatic cells, but not in germ cells
Karyotype with a male having Klinefelter syndrome (47,XXY)
The Barr, or sex chromatin, body is an inactive X-chromosome (Lyon’s hypothesis). It appears as a dense, dark-staining spot at the periphery of the nucleus of each somatic cell in the human female.
(1872)Huntington’s disease (H. chorea)…
- N < 26rpts→normal individual
- N = 27-35rpts → mutable alleles don’t cause disease, but show meiotic instability.
- N = 36-39rpts→reduced pentrance (late-onset) or non-pentrance.
- N ≥ 40-100rpts→ mutant
IQ is normal
ACH describes short-limb dwarfism due to mutations of fibroblast growth factor receptor-3 gene (FGFR3- 4p16.3)
neurological problems, lighter hair
and skin color, enhanced reflexes,
Autosomal Recessive diseases
due to a mutation of
due to a mutation in
LI patients suffer from palmoplantar keratoderma, often with painful fissures,
digital contractures, and loss of pulp volume. A nail dystrophy including ridging,
subugeal hyperkeratosis, or hypoplasia. Ectropion, eclabion (turning outward of
the eye lids and lip, respectively), scalp involvement, and loss of eye brows and
lashes seem to be more frequent in NCIE than in lamellar ichthyosis.
- DMD/BMD disease
- Limb girdle MD
- Spinal muscule atrophy
- Myotonic MD (AR)
- Facioscapulohumeral MDDuchenne Muscular Dystrophy…
An 8-y-old boy with D/BMD with enlarged calves
A dystrophin patient (7 y) and his younger brothers (1.5 y) diagnosed in the preclinical stage as D/BMD by the +ve family history and raised CPK level (2845 IU/L).
A) The Role of Proteins
B) Metabolic Pathways and Disease
1- Defects in amino acid metabolism
2- Defects in Carbohydrate metabolism
3- Defects in Nucleic acid metabolism
4- Defects in Lipid metabolism
C) Defects in Receptor Proteins
1- Hemoglobin Variants
- PKU - galactosemia - tyrosinemia
- Homocystinuria - MSUD.
- Jervis showed that the classical PKU was linked to PAH deficiency.
- Untreated galactosemia causes gastrointestinal disturbance, dehydration, loss of appetite, and lately cataracts and MR.
- Renal failure, spastic movement, MR, strong tendency for self-mutilation?!!
Fam. hypercholesterolemia (1/100,000).
- After 4-6 wk: presence of Y-chr → testis, while absence of Y-chr → ovary.
- Once testis development is initiated, two hormones are produced testosterone and MIH.
- Testosterone is converted to dihydrotestosterone (DHT) which develop the ex. genitalia.
- Absence of testis: → development of ovary.
* α1→ mild to heterozygotes, α1→ fatal to homozygous (complete ∆ of α-genes).
* α2 →intact to het, α2 →mild anemia to homozygous.
* βº gives very low β-globin protein due to splicing mutations during formation of mRNA (in splicing site).
e.g. height, weight, skin color, intelligence, blood pressure, many forms of behaviors.
Estimates of Heritability of various disorders