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Inquiry into LifeTwelfth Edition
Chapter 26
Lecture PowerPoint to accompany
Sylvia S. Mader
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
26.1 Counseling for Chromosomal Disorders
• Genetic Counselors
– Help individuals understand modes of inheritance
– Medical consequences of genetic disorders
– Inform individuals of possible decisions they may
need to make
26.1 Counseling for Chromosomal Disorders
• Karyotyping– A karyotype is a visual
display of individual’s chromosomes
– Can be performed on any babies, children, teens, adults and on a fetus
26.1 Counseling for Chromosomal Disorders
• Amniocentesis– A prenatal test– A sample of amniotic
fluid is collected– Fetal cells can be
isolated and analyzed– Risk of spontaneous
abortion is 0.25 - 0.5%
26.1 Counseling for Chromosomal Disorders
• Chorionic Villi Sampling– A prenatal test– Chorionic cells can be
collected and analyzed– Can be performed
earlier than amniocentesis
– Risk of spontaneous abortion is 0.5 - 1.0%
26.1 Counseling for Chromosomal Disorders
Normal Karyotype (male) Down Syndrome Karyotype
26.1 Counseling for Chromosomal Disorders
• Changes in Chromosome Number
– Too many or too few chromosomes
– Due to a process called nondisjunction
– Trisomy: An extra chromosome is carried
by an egg or sperm
– Monosomy: An egg or sperm lacks a
chromosome
Nondisjunction of Chromosomes During Oogenesis
Abnormal Autosomal Chromosome Number
Abnormal SexChromosome Number
26.1 Counseling for Chromosomal Disorders
• Changes in Chromosomal Structure– Chromosomal Mutations
– Radiation, certain chemicals, and some viruses can causes chromosomes to break apart
• Deletions• Duplications• Translocations• Inversions
26.1 Counseling for Chromosomal Disorders
• Chromosomal Mutations– Deletions
• Williams Syndrome– Chromosome 7 loses an end piece
» Individuals have a turned up nose and a wide mouth with small chin
» Poor academic skills but well-developed verbal and musical skills
• Cri Du Chat Syndrome– Chromosome 5 loses an end piece– Small head, mental retardation, cat-like cry
A Deletion
26.1 Counseling for Chromosomal Disorders
• Chromosomal Mutations– Duplication
• This example is characterized by poor muscle tone and autistic traits
26.1 Counseling for Chromosomal Disorders
• Chromosomal Mutations– Translocations
• The exchange of chromosomal segments between two nonhomologous segments
– A translocation of pieces of chromosomes 14 and 21 is another phenomena that results in Down syndrome (5% of all cases)
A Translocation
• Alagille Syndrome– Translocation of chromosomes 2 and 20
26.1 Counseling for Chromosomal Disorders
• Inversion– Segment is turned 180
degrees– Leads to altered gene
activity
26.2 Counseling for Genetic Disorders
• Family Pedigrees– Chart of Family’s History
• Key– Males are indicated by squares
– Females are indicated by circles
– Shaded means individual is affected by disorder
Pedigrees for Autosomal Disorders
Autosomal Recessive Autosomal Dominant
Autosomal Recessive Pedigree
Autosomal Dominant Pedigree
26.2 Counseling for Genetic Disorders
• Pedigrees for Sex-linked Disorders– X-linked disorders
• X-linked recessive disorders– To be affected, daughters must inherit it from both parents
– Sons can only inherit it from mother, therefore more males affected than females
• X-linked dominant disorders– Affected males pass the trait only to daughters
– Females can pass trait to both daughters and sons
– Y-linked disorders• Present only in males• Fathers pass trait to all sons
X-linked Recessive Pedigree
26.2 Counseling for Genetic Disorders
• Genetic Disorders of Interest– Autosomal Recessive Disorders
• Tay-Sachs Disease• Cystic Fibrosis (CF)• Phenylketonuria (PKU)• Sickle-Cell Disease
26.2 Counseling for Genetic Disorders
• Tay-Sachs Disease– Lack of Hex A enzyme– Results in defective
lysosomes (especially in the brain)
– Symptoms appear in the first year of life
– Disease is progressive and fatal
26.2 Counseling for Genetic Disorders
• Cystic Fibrosis– Most common genetic
disorder in Caucasians in U.S.
– Defect in chloride channel proteins in cells
– Thick, abnormal mucus production
• Lungs, bronchial tubes, pancreatic ducts affected
26.2 Counseling for Genetic Disorders
• Autosomal Recessive Disorders– Phenylketonuria
• Lack enzyme for phenylalanine metabolism• Affects nervous system development• Can usually be controlled with diet
– Sickle-cell anemia• Irregular red blood cells caused by abnormal hemoglobin
– Clog vessels- poor circulation
– Internal hemorrhaging
• Heterozygous individuals are normal unless dehydrated or experience mild oxygen deprivation
26.2 Counseling for Genetic Disorders
• Autosomal Dominant Disorders– Marfan Syndrome
• Defect in fibrillin-protein in elastic connective tissue– Long limbs and fingers, weakened arteries, dislocated lenses in
the eyes
– Huntington Disease• Progressive degeneration of brain cells• Gene for defective protein called Huntington
– Too many copies of the amino acid glutamine
26.2 Counseling for Genetic Disorders
• Incompletely Dominant Disorders– Familial hypercholesterolemia
• Affects the number of LDL-cholesterol receptors on cells– Homozygous for defective gene- has no receptors and develops
cardiovascular disease in teenage years– Heterozygous individual has half the normal number of receptors
26.2 Counseling for Genetic Disorders
• X-linked Recessive Disorders– Color Blindness
• About 8% of Caucasian males have red-green color blindness
– Duchene's Muscular Dystrophy• Absence of a protein called dystrophin
– Causes calcium to leak into muscle cells which actives enzymes that break down the cells
– Hemophilia• Hemophilia A is due to a lack of clotting factor VIII• Hemophilia B is due to a lack of clotting factor IX• Blood clots slowly or not at all
26.2 Counseling for Genetic Disorders
• Testing for Genetic Disorders– Testing for a Protein
• Some mutations lead to disorders caused by a missing enzyme
– Tay-sachs disease-test for quantity of hex A enzyme present in a sample of cells
» can determine if individual is homozygous normal, a carrier, or has Tay-sachs
– PKU-blood test done on all newborns to detect the presence of phenyalanine
Use of a Genetic Marker to Test for a Genetic Mutation
26.2 Counseling for Genetic Disorders
• Testing for Genetic Disorders – Testing the DNA
– Testing for genetic markers-similar to DNA fingerprinting
» Restriction enzymes cleave DNA
» Used to test for Huntington disease
– Testing with DNA probes
» DNA probe-single stranded piece of DNA that binds to complementary DNA
» For genetic testing, the probe has a mutation of interest
– DNA chip can test for many abnormalities at once
» Has many DNA segments
» mutated genes bind if present and are detected by laser scanner
Use of a DNA Chip
26.2 Counseling for Genetic Disorders
• Testing the Fetus– Ultrasound
• The fetus is exposed to high frequency sound waves to produce a picture
26.2 Counseling for Genetic Disorders
• Testing Fetal Cells– Amniocentesis
• Performed at 15 weeks of gestation • Can also test for alpha fetoprotein (AFP) which can indicate
neural tube defects
– Chorionic Villi Sampling• Performed earlier than amniocentesis • no amniotic fluid taken so cannot test for AFP
– Fetal Cells in Mother’s Blood• A small number of fetal cells enters the mother’s blood• These can be isolated and analyzed
26.2 Counseling for Genetic Disorders
• Testing the Embryo– Following in vitro fertilization, the embryo is allowed to
develop. At the 8-cell stage, a cell can be removed and tested.
– Only “normal” embryos are implanted
• Testing the Egg– Test the polar bodies of women who are
heterozygous prior to in vitro fertilization• If the polar body has the defect, then the ovum is normal
Counseling for genetic disorders: the present cont’d.
• Testing for genetic disorders cont’d.– Testing the embryo
• If both parents are carrier, they may want assurance that embryo is normal
– Following in vitro fertilization, can remove a cell at 6-cell stage and test for defect, then implant only those embryos that are normal
– Testing the egg• Test the polar bodies of women who are
heterozygous prior to in vitro fertilization– If the polar body has the defect, then the ovum is normal
26.3 Genomics
• Genomics is the Study of Genomes.– Humans have 20,000 - 25,000 genes that code for
proteins– Many other organisms have more genes than do
humans
26.3 Genomics
• Sequencing the Bases– The Human Genome project was a project to
sequence all of the base pairs in all of the DNA of human chromosomes.
• Genome Comparisons– Scientists can compare the genomes of different
species of organisms to gather data regarding the cause of many diseases.
26.3 Genomics
• The HapMap Project
– The objective is to catalog common sequence
differences that occur in human beings.
– People have been found to inherit patterns of
sequence differences, these are called haplotypes.
– Information gained from this project will allow
scientists to link haplotypes to the risk of specific
illnesses.
26.3 Genomics
• Proteomics and Bioinformatics– Proteomics
• Study of structure, function, and interaction of cellular proteins
• Translation of all human genes results in a collection of proteins called the proteome
• Computer modeling provides information about the three-dimensional shape of protein molecules
– May be possible to correlate drug treatment to genetic profiles
26.3 Genomics
• Proteomics and Bioinformatics– Bioinformatics
• Application of computer technologies to the study of the genome
• Analysis of data produced by genomics and proteomics• Cause and effect relationships between various genetic
profiles and genetic disorders caused by multifactor genes• Current genome includes gene “deserts” with no known
function– Bioinformatics may discover functions of these regions
26.3 Genomics
• Expanding Present-Day Genomics– The Human Genome is described as three-
dimensional• One dimension is the sections of DNA that encode proteins
– This accounts for less than 2% of the DNA
• A second dimension is what used to be called “junk” DNA– This “junk” DNA may code for RNA, researchers are trying to
determine what this RNA does
• A third layer of our genome lies outside DNA.– It consists of proteins and other chemicals that surround and
adhere to DNA. These may provide clues to the inheritance of certain diseases.
26.3 Genomics
• Gene Therapy– Insertion of genetic material into human cells for
treatment of a disorder– Ex vivo gene therapy
• Cells are removed from the patient– Treated outside the body and then returned to the patient
• Ex: SCID (Severe Combined Immunodeficiency)
– In vivo gene therapy• Patient is given a foreign gene directly• Gene is incorporated into the genome within the body• Ex: Cystic fibrosis
Ex Vivo Gene Therapy in Humans