GENETIC DISORDERS
 Genes code for specific proteins
 An allele that causes a genetic disorder codes for a malfunctioning protein or no
protein at all
 Mutation – any change in a gene that is accompanied by a loss or change in
functioning of the genetic information
 In most cases the alteration of a gene results in a recessive allele
 Mutagen- factors that cause mutations (ex. radiation)
 Mutations found in body cells (somatic cells) may go unnoticed unless a large
number of cells are affected
 Mutations found in sex cells (gametes) of a parent are more serious because these
can be passed on to create an organism that carries the mutation in every cell!
 Also these mutations can be passed on through several generations
Congenital Defects
 Defects visible at birth
 Can be genetic or environmental or both
***Genetic disorders can be the result of a gene defect or a chromosomal defect
Chromosomal Defects
 Ex. Cri-du-chat (deletion of part of chromosome #5)
Down syndrome (trisomy of #21)
Turner syndrome (XO – missing one sex chromosome)
Klinefelter syndrome (XXY- one extra X chromosome)
Recessively Inherited Disorders
 Many recessive disorders are inherited as simple recessive traits
 They range from non-lethal (albinism) to life-threatening (cystic fibrosis)
 Individuals who inherit both recessive alleles (one from each parent) will express the
disorder
Sickle Cell Anemia
 Autosomal recessive (caused by single gene)
 Affects 1/400 African Americans
 Caused by ONE amino acid substitution (caused by a change in one base pair in the
DNA sequence coding for this protein)
 affected protein is hemoglobin (oxygen-carrying protein)
 When the O2 content of an individual is low (physical stress/high altitude), this
results in “sickling” of rbc.
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Treatment is provided through transfusions and monitoring of lifestyle to avoid
overexertion
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About 1/10 Africans carries the sickle cell allele
Unusually high number of heterozygous individuals
Disease can be fatal in the recessive condition.
Studies revealed that children who were heterozygous for sickle cell anemia were
less likely to contract malaria and therefore more likely to survive to parenthood
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The malaria parasite spends part of its life cycle in red blood cells and the normal
shaped cells provide a perfect home
Thus, many homozygous dominant (unaffected) individuals often die of malaria (in
regions where it is common)
Heterozygous individuals produce enough normal rbc to meet their bodies’ oxygen
demands and enough sickled cells to reduce susceptibility to malaria (sickled cells
are fragile and thus interrupt the life cycle)
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Cystic Fibrosis
 Autosomal recessive (caused by single gene)
 Most common lethal disease in US (affects 1/2500 whites of European descent)
(1/25 = 4% of whites is a carrier)
 Normal allele codes for a membrane protein that functions in the transport of
chloride ion between certain cells and the extracellular fluid (ECF)
 Two recessive alleles results in absent or defective chloride channels
 Result is a build up of chloride ions outside cell (in ECF)
 This causes mucous that coats certain cells to become stickier than normal
 Mucus builds up in lungs, pancreas, digestive tract
 Causes infections and pneumonia
 Recent research indicates that extra-cellular chloride also disables natural antibiotic
made by body cells
 When the antibiotics go to the infected cells they are disabled and their remains just
adds to the mucous (a vicious cycle)
 Untreated, individuals will die before they are five years old
Treatment includes:
 -gentle pounding on chest to clear mucous from airways
 -daily doses of antibiotics to prevent infection
 -medication to help digest food
 -physical therapy to clear lungs
 In US, more than half of affected individuals survive into their late 20’s or beyond
 Location of gene responsible for cystic fibrosis was discovered in Toronto (Sick Kids
Hospital)
Huntington’s Chorea
 Autosomal dominant (single gene defect)
 Has no obvious phenotype until individual is about 35-45 years old
 Thus past reproductive age (may have already had children and passed on the
disease)
 Degenerative disease of the nervous system (brain cells die prematurely)
 Doctors have now developed a test to screen people with a family history of the
disease
 Debate - is it beneficial to find out that you have inherited a lethal and incurable
disease before it begins to affect you?
Hemophilia
 X-linked recessive
 Absence of one or more proteins responsible for blood clotting
 When a hemophiliac is injured, bleeding is prolonged because a firm clot is slow to
form
 Small cuts in skin are not usually a problem
 But bleeding in muscles or joints can occur without cause leads to pain and possible
serious damage
 Hemophilia has plagued the royal families in Europe (first hemophiliac seems to
have been Leopold (a son of Queen Victoria of England who was a heterozygous
carrier)
 Eventually brought to royal families of Spain, Russia through marriages of two of
Victoria’s daughters
 Treatment includes injections of the missing protein
Breast Cancer
 Cancer is uncontrolled cell division
 BRCA1 and BRCA2 are human genes that belong to a class of genes known as
tumor suppressors.
 These produce chemicals that inhibit the growth of tumors
 If a woman carries a defective copy there is an increased chance of developing
breast cancer
 6% chance with both functioning to 60% with only a single copy functioning
 Having the non-functioning gene does not for certain cause cancer and the
environment has a huge role in determining whether cancer genes are turned on
or off
Phenylketonuria
o An autosomal recessive disorder that results in the accumulation of
phenylalanine in the tissues and blood.
o 1 in 20,000 people have PKU
o If not treated, the brain function of a child with PKU does not develop properly,
and there is decreased body development and poor development of tooth
enamel
o Both parents must either have it or carry the trait to pass it on
o No known affected gene, screening occurs after birth
o Treatment includes a modified diet, low in protein
Genetic Testing
 Fetal testing (can reveal genetic problems)
 Includes amniocentesis and chorionic villus sampling (CVS)
Amniocentesis –between the 14th and 16th week of pregnancy
-syringe entered through uterus and extracts 10 mL of amniotic fluid (fluid
surrounding fetus)
-fluid analysis and karyotyping can determine some disorders
CVS
-small amount of tissue taken from placenta
-placenta contains cells of the chorionic villus which are rapidly reproducing
-within 24 h a karyotype can be produced
-can be performed between 8th and 10th week of pregnancy
Karyotype – a picture of an organisms chromosomes
- a method of organizing chromosomes according to number, size and type