Transcript Genetic Disorders

Genetic Disorders
Family Pedigrees
Definition
Presentation of family information in a
tree form using standardized symbols.
Purpose
Determination of how a trait is inherited
Determinations
Dominant or recessive
Autosomal or Sex Linked
GENETIC DISORDERS
Patterns of Inheritance
Autosomal recessive
Autosomal dominant
X-linked dominant
X-linked recessive
Y-linked
Mitochondrial inheritance
Autosomal Recessive
Definition
Inheritance of two defective alleles is required to express
the disorder.
Example
Cystic Fibrosis
Loci
7q31.2-31.3
Defect
Nonfunctional chloride channel in mucus, digestive,
and sweat glands
Result
Production of thick mucus and salty sweat
Effects
Malnutrition, pancreatic cysts, blocked airways
Cystic Fibrosis
Autosomal Recessive
Example
Sickle-cell Anemia
Loci
11p15.4
Defect
Abnormal RBC hemoglobin forming rods
Result
Fragile, crescent, sickle shaped cells
Affects
Anemia and clogged capillaries
Abnormal HbS molecule. Valine was added instead of Glutamate
GLUTAMATE
VALINE
Sickle Cell Anemia
Sickle Cell Anemia
AUTOSOMAL RECESSIVE
Albinism: absence of pigment in the skin
Galactosemia: high liver galactose
Phenylketonuria: high phenaylalanine in blood
Thalassemia: lack of hemoglobin production
Tay-Sachs: lack of gangliosides in nerve cells
AUTOSOMAL DOMINANT
Definition
Inheritance of only one defective allele is required to
express the disorder.
Example
Huntington‘s Disease
Loci
4p16.3
Defect
Trinucleotide repeats of CAG leading to polyglutamine
Mutated huntingtin neural protein leading to toxicity
Result
Degeneration of nervous system
Affects
Progressive dementia and death
Huntington’s Disease
Huntington’s Disease
Huntington’s Disease
AUTOSOMAL DOMINANT
Example
Marfan Syndrome
Loci
15q21.1
Defect
Mutated fibrillin connective tissue protein
Result
Weakened aortal connective tissue
Tall and thin with long arms, legs and fingers
Affects
Enlarged Aorta subject to rupture.
Marfan’s Syndrome
Marfan’s Syndrome
AUTOSOMAL DOMINANT
Familial hypercholesterolemia: high blood
cholesterol due to defective liver cell LDL
receptors
Hypercalcemia: high blood calcium due to
faulty parathyroid.
Nail-Patella Syndrome: absence of nails and
kneecaps.
X-Linked Recessive
Definition
Defect on one X Chromosome
. Females are carriers
. Males have disorder
Example
Examples
Color blindness
Loci
Xq28
Defect
Mutated opsin proteins in red and/or green cones
Result
Inability to bind to retinal during activation by light
waves
Affects
Inability to see red or green colors
Color Blindness
Color Blindness
Color Blindness
X-Linked Recessive
Duchenne Muscular Dystrophy
Loci
Xp21.1
Defect
Mutated dystrophin protein due to deletion of
exons
Result
Lack of attachment of dystrophin to the
sarcolemma (plasma membrane)
Affects
Weakness and wasting of muscle tissue due
to tearing of the sarcolemma.
Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
X-Linked Dominant
Definition
Defect on X chromosome
. Females have disorder
. Males have disorder
Examples
Coffin-Lowry Syndrome
Loci
Xp22.2-p22.1
Defect
Mutated serine/threonine kinase protein
Result
Lack of growth factor regulator phosphorylation
Affects
Craniofacial skeletal abnormalities
COFFIN-LOWRY SYNDROME
X-Linked Dominant
Incontinentia pigmenti
Loci
Xp11.2
Defect
Mutated melanin protein
Result
Lack of melanin deposition
Affect
Abnormal skin pigmentation
INCONTINENTIA PIGMENTI
Y-linked
Definition
Defect on Y chromosome
Examples
None
Loci
Y chromosome
Results
Loss of male fertility
Mitochondrial Inheritance
Mitochondria
Definition
Cytoplasmic organelles that make ATP
Genetic makeup
Carry 5-10 DNA molecules of 37 genes
Inheritance
From mothers to offspring through ovum
Results
Impaired energy conversion
Affects
Nerves, muscles, liver, and kidneys
Examples
Kearns-Sayre syndrome: short stature,
retinal degeneration
MERRF Syndrome: lack of energy transfer
VARTIATIONS IN CHROMOSOMAL
NUMBER
Types
Euploid
Normal chromosome number
Polyploid
Extra set(s) of haploid chromosomes
Aneuploid
Gain or loss of a single chromosome
POLYPLOID
ANEUPLOID
VARTIATIONS IN CHROMOSOMAL
NUMBER
Turner Syndrome (45,XO)
Definition
Inheritance of one X chromosome without a
partner X or Y chromosome.
Etiology
Paternal nondisjunction (75%)
Physical Features
Short and wide-chested
Small jaw
Webbed neck
Ovarian failure w/ lack of puberty
Underdeveloped sex characteristics
TURNER’S SYNDROME
VARTIATIONS IN CHROMOSOMAL
NUMBER
Klinefelter Syndrome (47, XXY)
Definition
Inheritance of two X chromosomes as well as one Y
chromosome.
Etiology
Maternal nondisjunction (60%)
Physical Features
Male with poor sex development
Breast development
Very low fertility
Degree of subnormal intelligence
KLINEFELTER SYNDROME
VARTIATIONS IN CHROMOSOMAL
NUMBER
Jacobs Syndrome (47,XYY)
Definition
Inheritance of two Y chromosomes as well
as one X.
Etiology
Paternal nondisjunction during meiosis II
Physical Features
Above average height
Degree of subnormal intelligence
JACOB’S SYNDROME
VARTIATIONS IN CHROMOSOMAL
NUMBER
Poly-X (Meta) Females (XXX, XXXX)
Definition
More than two X chromosomes
Etiology
Maternal nondisjunction
Physical Features
Long legs and slender torsos
Normal sexual characteristics
Meta Female karyotype
Trisomy 23
Hermaphroditism
Definition
Individuals with both ovarian and testicular
tissue.
Etiology
Mosaicism
Cells of two kinds (XX & XY)
Sex Chromosome Crossing Over
Exchange of testis determining factor (TDF)
from the Y chromosome
MOSAICISM
MOSAIC EXPRESSION
TESTES DETERMINING FACTOR
Hermaphroditism
Physical Features
Mosaicism
Male features dominate
Sex Chromosome Crossing Over
Female:
XY without TDF
Male:
XX with TDF
Androgen Insensitivity
Definition
XY individuals develop as phenotypic females
Etiology
Androgen receptor gene mutation
Loci
Xq11-13
Results
Lack of interaction between cell and
testosterone
Physical Features
Lack of normal female reproductive tract
Well-developed breasts
Little pubic hair
ANDROGEN INSENSITIVITY