 What’s a “mutagen”?  What does a mutation do to DNA?  If a mutation affects a gene, then what might happen to the protein sequence?

 Some genetic disorders are caused by mutations and errors in the DNA code GENETIC DISORDERS

 Point mutation: a single base pair is substituted for another (ex. A  C) TYPES OF MUTATIONS

 Insertion/deletion: results in a “frameshift” mutation (how codons are read, ordered, or sequenced) TYPES OF MUTATIONS

 Large scale mutations: duplications/deletions of large chromosome sections; inversions that reverse gene sequences; translocations that exchange parts of nonhomologous chromosomes TYPES OF MUTATIONS

 In autosomal dominant disorders, you only need 1 copy of the allele to have the disease/trait AUTOSOMAL DOMINANT DISORDERS

 A neurodegenerative genetic disorder where nerve cells slowly break down HUNTINGTON’S DISEASE

 Results in uncontrollable muscle movements and mental deterioration HUNTINGTON’S DISEASE

 Caused by a defect on the 4 th chromosome where the triplet CAG repeats more times than it should – the more triplets, the earlier the onset of the disease HUNTINGTON’S DISEASE

 Symptoms normally don’t appear until age HUNTINGTON’S DISEASE

 If you found out that one of your parents has Huntington’s disease, would you choose to be tested for it yourself? (Yes or No) BIOETHICS QUESTION OF THE DAY

 If you found out that you, yourself, have Huntington’s disease, would you choose to have children? (Yes or No) BIOETHICS QUESTION OF THE DAY

 In autosomal recessive disorders, you need two copies of the allele in order to have the disease/trait AUTOSOMAL RECESSIVE ALLELES

CYSTIC FIBROSIS  Defective allele on chromosome 7 results in a faulty protein  Causes a thick, heavy mucus to build up and clog the lungs.

Need two recessive alleles - people with one normal chromosome produce enough of the correct protein CYSTIC FIBROSIS

People with cystic fibrosis have problems breathing and digesting and are more vulnerable to lung infections

CYSTIC FIBROSIS  Approximately 30,000 children and adults in the U.S. have cystic fibrosis.  About 1 in every 31 Americans are carriers of the defective CF gene, but do not have the disease.  CF is most common in Caucasians, but it can affect all races. (via the Cystic Fibrosis Foundation)

 Red blood cells form a bent shape because of misshapen hemoglobin (carries oxygen in the blood) SICKLE-CELL ANEMIA

 People with sickle-cell suffer from painful episodes, fatigue, shortness of breath, and other health problems (hemoglobin carries oxygen in the blood).

 One single base change to the normal allele results in sickled-cells. SICKLE-CELL ANEMIA

 One single base change to the normal allele results in sickled-cells. SICKLE-CELL ANEMIA

 Malaria is a mosquito-transmitted disease caused by a parasite that infects red blood cells,  More common in central parts of Africa, South America, and southern Asia. SICKLE-CELL AND MALARIA

 People who are heterozygous for the trait (who have only one sickle-cell allele) are resistant to malaria but still have enough hemoglobin to function well. SICKLE-CELL AND MALARIA

 A disease where the body cannot break down the amino acid phenylalanine PHENYLKETONURIA (PKU)

 A missing enzyme causes phenylalanine to build up in the body; can eventually cause brain damage if the disease is not managed PHENYLKETONURIA (PKU)

 Build of lipids in the central nervous system (CNS) – usually causes death by age 4 TAY-SACHS DISEASE

 More common in specific populations TAY-SACHS DISEASE

 Colorblindness  Decreased ability to see or distinguish between certain colors  Red-green colorblindness, blue-yellow colorblindness EXAMPLES OF X-LINKED DISORDERS

 Decreased ability to see or distinguish between certain colors  Red-green colorblindness, blue-yellow colorblindness EXAMPLES OF X-LINKED DISORDERS

 Hemophilia  A bleeding disorder that prevents blood from clotting properly  The person bleeds more than someone without hemophilia

EXAMPLES OF X-LINKED DISORDERS  Duchenne Muscular Dystrophy  A disorder that involves rapidly increasing muscle weakness and loss of muscle tissue

 Moving on…

 Some genetic disorders are caused by chromosomal mutations GENETIC DISORDERS

 A karyotype allows you to see all of the chromosomes in a single cell of an organism GENETIC DISORDERS

 With a karyotype, you can easily observe if there are any extra/missing chromosomes. GENETIC DISORDERS

How many chromosomes do normal humans have? 46 KARYOTYPES

How many are autosomal chromosomes? 44 KARYOTYPES

How many are sex chromosomes (determine sex of the organism?) 2 KARYOTYPES

 Looking at a karyotype, we can very easily observe if the organism has any extra or missing chromosomes that can result in certain genetic disorders. KARYOTYPES

 “not coming apart”  The most common error in meiosis  Occurs when homologous chromosome pairs fail to separate during anaphase I or II, resulting in a sex cell with an extra or missing chromosome. NONDISJUNCTION

1. Down Syndrome (Trisomy 21)  Three copies of chromosome 21 NONDISJUNCTION DISORDERS

2. Turner’s Syndrome (X)  Only one copy of the X chromosome (no Y) NONDISJUNCTION DISORDERS

3. Klinefelter’s Syndrome (XXY)  Two copies of the X chromosome and a Y NONDISJUNCTION DISORDERS

 A diagram that shows the inheritance pattern of a trait over many generations is called a pedigree. PEDIGREES

HOW TO READ A PEDIGREE Male Female Pedigree Symbols Children/ Marriage Siblings I II III Affected Carrier Person

 Looking at a family pedigree, we observe how certain traits have been passed down from parents to offspring and also how certain traits and genetic disorders are expressed. HOW TO READ A PEDIGREE

How many males vs. females are affected? Autosomal Dominant = EQUAL AUTOSOMAL DOMINANT INHERITANCE

Does it skip generations? Autosomal Dominant = NO AUTOSOMAL DOMINANT INHERITANCE

Who does not express the trait? Autosomal Dominant = Homozygous recessive individuals AUTOSOMAL DOMINANT INHERITANCE

How many males vs. females are affected? Autosomal Recessive = EQUAL AUTOSOMAL RECESSIVE INHERITANCE

Does it skip generations? Autosomal Recessive = YES AUTOSOMAL RECESSIVE INHERITANCE

Who does not express the trait? Autosomal Recessive = Either sex, with at least one dominant allele AUTOSOMAL RECESSIVE INHERITANCE

How many males vs. females are affected? Sex-linked Recessive = MORE MALES X-LINKED RECESSIVE INHERITANCE

Does it skip generations? Sex-linked Recessive = Yes, but all affected men will inherit trait from mothers X-LINKED RECESSIVE INHERITANCE

Who does not express the trait? Sex-linked Recessive = Female carriers X-LINKED RECESSIVE INHERITANCE

X-LINKED INHERITANCE: A CASE STUDY