Transcript genetic disorder

Disorders and other genetic
traits
Bio II
Chromosomal Inheritance
All but one pair of chromosomes in males
and females are the same.
– Autosomes - Nonsex chromosomes
The different pair, sex chromosomes,
determines the sex of an individual.
– X-linked (sex-linked) is the term used for
genes carried on the X chromosome.
X-Linked Alleles
X-linked alleles have a different pattern of
inheritance than alleles on autosomes
because the Y chromosome is blank for
these alleles.
– Inheritance of a Y chromosome cannot offset
the inheritance of an X-linked recessive allele.
Human X-Linked Disorders
Color Blindness
– In humans, color vision receptors in the retina
are three different classes of cone cells.
Only one type of pigment is present in each class
of cone cell.
– The allele for blue-sensitive is autosomal, but the redand green-sensitive proteins are on the X chromosome.
Color Blindness
Human X-Linked Disorders
Muscular Dystrophy
– Absence of protein dystrophin allows calcium
to leak into muscle cells.
Hemophilia
– Hemophilia A due to lack of clotting factor IX
and hemophilia B due to lack of clotting factor
VIII.
X-Linked Recessive Inheritance
Males show disorder more
than females
Son cannot inherit
disorder from his father
Human Genetic Disorders
Autosome - Any chromosome other than a
sex chromosome.
– When a genetic disorder is autosomal dominant,
an individual with AA or Aa has the disorder.
– When a genetic disorder is autosomal recessive,
only aa individuals have the disorder.
Carriers - Individuals unaffected by a disorder but can
have an affected child.
Autosomal Recessive Disorders
Tay-Sachs Disease
– Progressive deterioration of psychomotor functions.
Cystic Fibrosis
– Mucus in bronchial tubes and pancreatic ducts is
particularly thick and viscous.
Phenylketonuria
– Lack enzyme for normal metabolism of phenylalanine.
Clinical Features
Cystic fibrosis is a heterogeneous
recessive genetic disorder with features
that reflect mutations in the cystic
fibrosis transmembrane conductance
regulator (CFTR) gene.
Classic cystic fibrosis is characterized by
chronic bacterial infection of the airways
and sinuses, fat maldigestion due to
pancreatic exocrine insufficiency,
infertility in males due to obstructive
azoospermia, and elevated
concentrations of chloride in sweat.
Patients with nonclassic cystic fibrosis
have at least one copy of a mutant gene
that confers partial function of the CFTR
protein, and such patients usually have
no overt signs of maldigestion because
some pancreatic exocrine function is
preserved.
Treatment
•The only way to cure CF would be to use gene therapy to replace the
defective gene or to give the patient the normal form of the protein before
symptoms cause permanent damage.
•The major goal in treating CF is to clear the abnormal and excess
secretions and control infections in the lungs, and to prevent obstruction in
the intestines.
•For patients with advanced stages of the disease, a lung transplant
operation may be necessary.
•Although treating the symptoms does not cure the disease, it can greatly
improve the quality of life for most patients and has, over the years,
increased the average life span of CF patients to 30 years.
Gastrointestinal Treatment
Modified diet
Due to pancreatic disorders, children with CF require a modified diet, including
vitamin supplements (vitamins A, D, E, and K) and pancreatic enzymes.
Maintaining adequate nutrition is essential. The diet calls for a high-caloric
content (twice what is considered normal for the child's age), which is typically
low in fat and high in protein. Patients or their caregivers should consult with
their health care providers to determine the most appropriate diet.
Gene Therapy
Gene therapy is the use of
normal DNA to "correct" for
the damaged genes that
cause disease.
In the case of CF, gene
therapy involves inhaling a
spray that delivers normal
DNA to the lungs.
The goal is to replace the
defective CF gene in the
lungs to cure CF or slow
the progression of the
disease.
Autosomal Dominant Disorders
Neurofibromatosis
– Tan or dark spots develop on skin and darken.
Small, benign tumors may arise from fibrous
nerve coverings.
Huntington Disease
– Neurological disorder leading to progressive
degeneration of brain cells, in turn causing
severe muscle spasms and personality
disorders.
Huntington Disorder
Autosomal dominant allele
Causes involuntary movements, nervous system
deterioration, death
Symptoms don’t usually show up until person is
past age 30
People often pass allele on before they know
they have it
Achondroplasia
Autosomal dominant allele
In homozygous form usually
leads to stillbirth
Heterozygotes display a
type of dwarfism
Have short arms and legs
relative to other body parts
Niemann-Pick Disease
Infant symptoms include
jaundice, difficult feeding,
enlarged abdomen, and
pronounced mental retardation.
The Disease
Condition involving the breakdown and use of fats and
cholesterol in the body
Harmful amounts of lipids accumulate in the spleen,
liver, lungs, bone marrow, and brain
Autosomal recessive pattern of inheritance (two copies of
the gene must be present)
Four variants: A, B, C1, and C2
Clinical feature include: severe liver disease, breathing
difficulties, developmental delay, seizures, increased
muscle tone, lack of coordination, problems feeding, and
inability to move eyes vertically.
No treatment
5. HOW CAN GENETIC
DISORDERS BE
DETECTED?
Prenatal Diagnosis
Amniocentesis
Chorionic villus sampling
Fetoscopy
All methods have some risks
Studying Human Genetics
Studying Human Genetics is much more
complicated than using other model systems
(e.g. Pea Plants)
–
Humans reproduce slowly, have few offspring, and it
is unethical to breed humans for experiments
There are many techniques that are used to
study human genetics indirectly
–
–
–
Karyotypes
Pedigree analysis
Linkage maps
Prenatal Diagnosis
Amniocentesis
Chorionic villus sampling
Karyotype
Picture of an individual’s
chromosomes
Making a Karyotype:
– Metaphase chromosomes are fixed
and stained
– Chromosomes are photographed
through microscope
– Photograph of chromosomes is cut up
and arranged to form karyotype
diagram
Karyotype
Autosomes
Sex Chromosomes
male
Pedigree
Symbols
female
marriage/mating
offspring in order of birth,
from left to right
Individual showing trait
being studied
sex not
specified
I, II, III, IV...
generation
male
Pedigree
Symbols
female
marriage/mating
offspring in order of birth,
from left to right
Individual showing trait
being studied
sex not
specified
I, II, III, IV...
generation
Human Genetic Conditions
A genetic abnormality is an uncommon or rare
trait
– E.g. Polydactyly
A genetic disorder is an inherited condition that
may cause medical problems
– E.g. Cystic Fibrosis
A syndrome is a set of symptoms that
characterize a disorder
– E.g. Down Syndome
Human Genetic
Abnormalities/Disorders
Different patterns of inheritance are
observed depending on the condition:
– Autosomal Recessive Inheritance
– Autosomal Dominant Inheritance
– X-linked inheritance
Autosomal Recessive
Inheritance
If parents are both
heterozygous, child will
have a 25% chance of
being affected