Classic Methods of Genetic Analysis 1.Isolation of mutants and experimental crosses to see inheritance patterns 2.Organism of study: bacteria, viruses, fruit flies, and mice –a.Short life cycle, lots of offsprings 3.Do not work for humans: –a.Ethics –b.Long life cycle, few offsprings –c.Use alternative methods

Genetic Counseling Done at most major hospitals Visit counselor if you have relatives or children with a genetic disorder or have had a baby die or been still born Deals with probabilities, not absolute

Genetic Screening Systematic testing of fetuses, newborn children or individuals of any age to determin potential genetic handicaps

Prenatal screening A.Amniocentesis 1.Detect chromosomal abnormalities and other disorders if coupled with biochemistry test and/or rDNA techniques 2.Ultrasound locates fetus 3.Hyperdermic needle inserted into amnion to withdraw cm 3 of amniotic fluid 4.Isolate and culture fetal cells, and subject cells to a # of test 5.Usually administered between weeks 14-16

Genetically “normal” Our genotypes contain about 100,000 loci, 10% of which may be polymorphic Parents of a child with a genetic disorder look just like the rest of us, the combination of the two just happens to bring together 2 rare recessive alleles All of us are carriers (heterozygous) of several genetic disease Risk of meeting and having children with someone who has the same rare allele is minute

Human Genetic Diseases

What is inherited disease? Due to rare genotypes that produces illadapted phenotypes in environments in which more common genotypes give rise to healthy phenotypes The majority of human genes, and therefore the majority of genetic disorders are carried on the autosomes

Mutations Mutations are changes in the genetic material. There are 2 kinds of mutations 1. Chromosomal Mutations: involve segments of chromosome, whole chromosome, or entire sets of chromosome 2. Gene Mutations: involve individual genes

Chromosomal Mutations Usually so serious that carriers cant reproduce Complex syndromes because it involves many, many genes Detected using Karyotyping analysis

Karyotyping Analysis 1.Obtain cells by amniocentesis 2. Stimulate mitosis with phytohemagglutinin 3. Arrest cells during metaphase using colchicine 4. Stain and photograph under microscope 5. Cut up photo and arrange homologous chromosomes

Two forms of chromosomal defects 1.Changes in number of chromosome 2.Structural abnormalities in chromosomes

Aneuploidy Changes in the number of chromosomes The suffix used is -somy Caused by an error in cell division Trisomy: three copies of a chromosome Monosomy: one member of a pair, usually lethal

Aneuploidy autosomol Disorders (chromosomal number disorder)

1. Down Syndrome caused by the presence of an extra copy of chromosome 21 (trisomy 21) It results in heart and circulatory problems, a weakened immune system and mental retardation. Some characteristics include a flattened face, poor muscle tone, and short stature The degree of retardation varies greatly. 1/700 births, risk increases w/ age of parent

Aneuploidy of the sex chromosomes

1. Turner’s Syndrome XO 1/3000 live births 20% of spontaneous abortions Short female, deficient sexual development (YO is lethal probably b/c X carries genes for clotting factor)

2. Klinefelter’s Syndrome XXY 1/500 males Underdeveloped testes, infertile Long legs, possible breast development, high pitched voice

3. Triple X XXX Rare, usually normal Possible retardation and limited sexual development

Structural abnormalities in chromosomes 1.Translocation: chromosomes exchange pieces 2.Inversion: reversal of a chromosome segment 3.Deletion: loss of a chromosome segment 4.Duplication: 2 copies of a segment

Autosomal Dominant Disorders Biochemical basis is poorly understood Over 1700 traits

1. Huntingtons Chorea Produced by a single dominant allele located on chromosome number 4. People who have this disease show no symptoms until they are in there thirties or forties, when the gradual damage to their nervous system begins. They suffer a painful progressive loss of muscle control and mental function until death occurs. No known treatment

Autosomal Recessive Disorders Likely due to mutations which produce alleles that encode defective enzymes Over 1300 traits

1. Cystic Fibrosis the most common fatal disease in the US amongst whites. Caused by a recessive allele on chromosome 7 causes the lungs and breathing pathway to become clogged due to interference with the movement of chloride ions in and out of the cell. Short life expectancy

2. Phenylketonuria (PKU) Absence of enzymes phenylalanine hydroxylase causes increased levels of phenylalanine in blood and tissue Causes mental retardation, epilepsy, restlessness, and muscle stiffness Children tested at birth are put on diets low in phenylalanine

3. Sickle Cell Anemia A blood disorder characterized by a sickled shape blood cells. Caused by a point mutation where valine replaces glutamic acid in hemoglobin In the US, this disorder is most common among blacks. 100,000 deaths per year

4. Albinism Caused by a recessive allele on chromosome 11. People with this disorder have no pigment in their hair or skin Must avoid excessive exposure to bright sunlight because they lack melanin

5. Tay-Sachs Fatal disorder most common amongst Medetar Jewish communities. Children with Tay-Sachs suffer from rapid breakdown of the nervous system beginning at age 2 or 3.

Sex linked Disorders 250 traits, mostly recessive

1. Colorblindness recessive disorder in which a person cannot distinguish between certain colors. Most types of colorblindness are caused by sex-linked genes located on the X chromosome

2. Hemophilia recessive allele on the X chromosome. In hemophilia, the protein antihemophilic factor (AHF) necessary for normal blood clotting is missing. Affects about 1/10,000 males and 1/100,000,000 females. People with hemophilia can bleed to death from seemingly minor cuts and may suffer from internal bleeding from bumps or bruises. It can be treated by injecting AHF into the patients.

3. Duchenne Muscular Dystrophy An inherited disease that results in the progressive wasting away of skeletal muscle. Children with MD rarely live past early adulthood.Wheelchair by age 10, death by age 20 The most common form of MD is caused by a defective version of the gene that codes for a muscle protein known as dystrophin. This gene is located on the X chromosome 1/5000 live male births No cure