CHAPTER 14 THE HUMAN GENOME

Human Heredity INTRODUCTION Humans have 46 chromosomes made of DNA & protein autosomes – 44 of the 46 sex chromosomes – either XX (female) or XY (male). eggs carry only X chromosome. ½ of sperm carry X ½ of sperm carry Y

Human Heredity Karyotype Photograph of chromosomes of cells during mitosis. Amniocentisis – how cells are gotten for a karyotype. Long needle is inserted right into where the baby is developing (amniotic sac). Done between 15-20 weeks of pregnancy SEE FIG. 14-1, pg. 341 - karyotype of a male. Used to see if there is a chromosomal disorder in a baby. Can detect disorders like Down’s Syndrome, Kleinfelter’s Syndrome, Turner’s Syndrome.

Human Traits Scientists try to identify inherited traits controlled by one gene. Must make sure the trait is controlled by the gene and not influenced by the environment. Pedigree – a chart used to study how a trait is passed from one generation to another in a family. Fig. 14-3 Carrier – an individual who carries one allele for a trait and is not affected by that gene.

Human Traits Cont’d Impossible (almost) to associate one gene with one trait for two reasons: Polygenic – controlled by many genes. Shape of eyes, ears, hair color, etc. Environmental influence. Nutrition, exercise. Height – determined by genetic factors, but strongly influenced by environment (nutrition, etc.) Today, humans are approx. 10cm taller than in the 1800’s. Even though environment influences genes, that does not mean that those genes can’t reach their full expression in future generations.

Human Genes DNA sequence determines characteristics Sequence of nucleotides Studying is difficult because: Length between generations Very few offspring are produced.

Human Genes Cont’d ABO blood group 3 alleles for this gene – IA, IB and I IA & IB are codominant i is recessive. alleles produce antigens immune system recognizes giving the “blood type”. IAi - Blood type “A” IBi – Blood type “B” IAIB – Blood type “AB” ii – Blood type “O” SEE FIG 14-5, pg. 344

Rh FACTOR + or – part of a person’s blood type. found through the rhesus monkey single gene with two alleles (+ or -) Rh+ is dominant Rh- is recessive. RHESUS MONKEY

RECESSIVE GENETIC DISORDERS PKU – PHENYLKENTONURIA lack enzyme to breakdown amino acid phenylalanine. found in foods like, milk, sugar substitutes, etc. builds up and causes mental retardation. A diet low in phenylalanine will prevent the effects All newborns are tested for this. allele is found on chromosome 12.

TAY-SACH’S DISEASE Found mostly in people of Jewish descent from central and eastern Europe. Enzyme lacking that breaksdown lipids in the brain. Children die within 5 – 7 years of life. No treatment Can learn the probability of having a child with the disorder by genetic testing. Recessive disorder.

DOMINANT DISORDERS Expressed no matter what only need one copy of the gene. Achondroplasia form of dwarfism Huntington’s Disease progressive loss of muscle control and mental function. No symptoms until middle age.

DISORDERS CAUSED BYCHANGES IN THE DNA SEQUENCE. Sickle – Cell Disease Causes the red blood cells to turn into a “sickle” shape. Blood cells can’t fit through the small vessels. Causes pain. Affects 1 in 500 African Americans .

CYSTIC FIBROSIS (CF) Most common in Northern Europe descendents. Patients now live past their 20’s. Caused by the deletion of 3 bases 1 amino acid Causes the protein to fold incorrectly and it is destroyed. The malfunction of the protein does not allow chloride ions to move across membranes. Over production of mucous Serious problems in the digestive system and lungs. It is a recessive disorder.

SEX-LINKED DISORDERS More than 100 sex-linked disorders mapped to the X chromosome. Males only receive one X, so they are more susceptible to sex-linked disorders. Males pass defective X chromosome to their daughters who are then “carriers” and can pass it to their sons. Seems to “skip a generation”

COLOR-BLINDNESS 3 genes on the X chromosome responsible for seeing in color. Defect in any of the 3, results in some form of colorblindness. Most common red-green – can’t see red and green. Found in 1 of 10 males in the US Females need 2 defective X chromosomes to be colorblind only 1 in 100 in US.

Hemophilia x-linked disorder where the protein that makes blood clot is missing. Patients can bleed to death from a simple cut or bruise. 2 genes control blood clotting on the X chromosome. Defect in either gene results in hemophilia. Affects 1 in 10,000 males Coagulation Factor VIII

Duchenne Muscular Dystrophy x-linked disorder where there is a weakening of muscles. Patients rarely live into adulthood. Defect in the gene on the X-chromosome that codes for muscle protein. 1 in 3,000 males is affected in the US

Chromosomal Disorders (whole chromosome) Down Syndrome – autosomal genetic disorder caused by nondisjunction of chromosome # 21. Trisomy – three copies of one chromosome Most common form of trisomy – 3 copies of chromosome #21. Causes mild to severe mental retardation Patients are usually sterile characterized by an asian-looking face. Usually die of heart problems in their 40’s. See. Fig. 14-16, pg. 353.

Turner’s syndrome Nondisjunction of the X chromosome. Females only have one X chromosome XO Females are sterile and very short, but otherwise are normal females.

Kleinfelter’s syndrome Nondisjunction of the X chromosome Males are XXY. Males are sterile and suffer from mental retardation.

Human Molecular Genetics Human DNA Analysis 6 billion base pairs in the DNA sequence. Biologist search the genome using base pair sequence in the DNA .

Testing for Alleles Can label DNA to see specific sequences. This can test parents to see if they are a carrier for a genetic disorder like cystic fibrosis or Tay-Sach’s. Done using small fragments of DNA & checking the length of the fragments. Use restriction enzymes to cut the DNA into fragments.

Testing for Alleles Used to identify an individual because no two organims share the exact same DNA (except identical twins) DNA is cut with restriction enzymes into fragments. Fragments are separated by their size using gel electrophoresis.

DNA Fingerprinting Some fragments show great differences (variability) and are detected using a DNA probe. Called “restriction length polymorphisms” or RFLP fragments separate and create bands that can be read by scientists and identify an individual. Samples of DNA can be gotten from blood, hair, sperm, skin, etc. See Fig. 14-18, pg. 356

The Human Genome Project Dr. James Watson & Dr. Francis Collins – begun in 1990 Wanted to map the entire human genome. 1996- E. coli was mapped. 2000 – Sequencing of the human genome was completed. Contains between 31,000 – 37,000 genes.

The Human Genome Project This information could one day be used: commercially; biotechnology could provide: new drugs treatments for disease based on a person’s genetic code.

Gene Therapy Absent or abnromal gene is replaced by a normal gene. Correct the protein or enzyme 1999 – French girl was “cured” of a genetic immune disease “Changed” her bone marrow cells and then placing them back into her body.

Gene Therapy Viruses are used to modify genes. Incorporate their DNA into a host’s DNA. Cannot cause disease. The correct gene is spliced into the virus’s DNA The “corrected” gene is put into the patient Incorporated into the DNA, correcting the protein/enzyme. Still very experimental and has not had much success yet.

Ethical Issues in Human Genetics Questions as to how genetic information should be used: Who should have access to your genetic information? Should humans be “designed”? Should information on the probability of a person getting a disease (ex. Heart disease) be shared with insurance companies or employers? Should any person arrested for any reason have to submitted a sample of their DNA for use in a criminal library? This is already being done.