Human Genetic Mutations

2 Main Types of Mutations 1.) Chromosomal Mutations 2.) Gene Mutations

What are chromosomes? Humans have 23 pairs of chromosomes, with one chromosome from each parent. The chromosomes are coiled up DNA. Under normal conditions all of the chromosomes are inherited in tact. This is a normal karyotype of human chromosomes. A karyotype is a picture of chromosomes lined up to look at and compare.

Chromosomal Mutations Any change in the structure or number of chromosomes Large scale: Affect many genes

5 Types Deletion Duplication Inversion Translocation NonDisjunction

One or more genes are removed Chromosomal Deletion One or more genes are removed Causes: Wolf-Hirschhorn syndrome (severe mental retardation) cri du chat syndrome (meowing sounds, mental retardation)

Wolf-Hirschhorn syndrome (WHS) refers to a condition that is caused by a missing part (deletion) of the short arm of chromosome 4.

Chromosomal Duplication A segment of genes is copied twice and added to the chromosome Causes: Charcot–Marie–Tooth disease (high arched foot, claw feet, confined to a wheelchair)

Chromosomal Inversion a segment of genes flip end-to-end on the chromosome Causes: Four-Ring Syndrome (cleft palate, club feet, testes don’t descend)

Chromosomal Translocation Material is swapped with another chromosome Causes: Burkitt’s Lymphoma (cancer of the lymph nodes, in children)

Nondisjunction Chromosomes FAIL TO SEPARATE during meiosis Meiosis I Nondisjunction Meiosis II Nondisjunction

Nondisjunction Produces gametes (and therefore a baby) with one missing chromosome or one extra chromosome

Nondisjunction (in Meiosis II)

Fertilization

Nondisjunction Every cell in that baby’s body will have __ copies of this chromosome instead of___. This condition is called ____________. Trisomy 21 = Individual has _____ copies of chromosome # ________

Nondisjunction Every cell in that baby’s body will have 3 copies of this chromosome instead of 2. This condition is called __________. Trisomy 21 = Individual has _____ copies of chromosome # ________

Nondisjunction Every cell in that baby’s body will have 3 copies of this chromosome instead of 2. This condition is called TRISOMY Trisomy 21 = Individual has __ copies of chromosome # ____.

Nondisjunction Every cell in that baby’s body will have 3 copies of this chromosome instead of 2. This condition is called TRISOMY Trisomy 21 = Individual has 3 copies of chromosome # 21.

Chromosomal Mutations Most chromosomal mutations are lethal If the fetus survives: Tend to cause wide-spread abnormalities Example: Down Syndrome

Down Syndrome Cause: Nondisjunction of chromosome 21 Three copies of chromosome 21 = “TRISOMY 21”

One in every 691 babies in the the United States is born with Down syndrome, making Down syndrome the most common genetic condition. Short stature (height) Low muscle tone A short, wide neck. Slanted eyes. Irregularly shaped mouth and tongue. Intellectual disability Heart defects

Genetic Screening - Amniocentesis

Karyotypes A pictorial display of metaphase chromosomes from a mitotic cell Homologous chromosomes- pairs Chromosomes pairs 1-22 are called autosomes Chromosome pair 23 are called the sex chromosomes

Trisomy 21 - Down Syndrome

Klinefelter’s Syndrome Due to nondisjunction Chromosome makeup is XXY Creates a sterile male

Turner’s Syndrome Due to nondisjunction Monosomy- the condition in which there is a missing chromosome. Sex chromosome make up is X only Females that will not undergo puberty.

Edward’s Syndrome Due to nondisjunction Extra number 18 chromosome (trisomy 18) Traits: Low ears, kidney and heart defects

Patau’s Syndrome Extra number 13 chromosome (trisomy 13) Traits: Deformed eyes, ears and lips, polydactyly (extra fingers or toes)

Too much or too little DNA is bad! KEY POINT #1 Too much or too little DNA is bad!

Gene Mutations Small scale: one gene is affected Any change to the DNA sequence of a gene: Nucleotides/Bases may be added, missing, or changed

Gene Mutations: 2 Types Point Mutation Frameshift Mutation

Point Mutation One base (A, T, C, or G) is substituted for another Can Cause: Sickle-cell anemia 3 Possible Consequences: nonsense mutations: code for a stop, which can translate the protein missense mutations: code for a different amino acid silent mutations: code for the same amino acid

Frameshift Mutation One or more bases (A, T, C, or G) are added or deleted Can Cause: Cystic Fibrosis Caused by: Insertion: adding a base Deletion: removing a base

Causes of Mutations spontaneous occur during DNA replication Caused by MUTAGENS physical ex: radiation from UV rays, X-rays or extreme heat chemical (molecules that misplace base pairs or disrupt the helical shape of DNA).

Gene Mutations KEY IDEA: A mutated gene will make a mutated protein

Example: Sickle Cell Anemia Normal Red Blood Cell Red blood cells shaped like a disc Hemoglobin (protien) carries oxygen to all parts of the body Sickle Red Blood Cell Red blood cells form an abnormal crescent shape Hemoglobin (protein) is abnormally shaped don't move easily through your blood vessels form clumps and get stuck in the blood vessels Mutation located on Chromosome 11 Effects mostly African Americans

Example: Cystic Fibrosis (CF) What is it? Autosomal, recessive disorder found on Chromosome 7 Symptoms Thick mucus in the lungs and digestive track Constant lung infections and impaired digestion

Cystic Fibrosis (CF) Who gets it? Most common in Caucasians Prevalence 1 in ~3,000 Americans has CF 1 in 23 white Americans carries the mutant allele!

Cause of Cystic Fibrosis (CF) The “CFTR” gene is mutated 3 base pairs are deleted Mutant protein is missing an amino acid and cannot fold correctly vs

Albinism Due to the lack of the pigment melanin (a protein) in the skin, eyes, and hair.

Hemophilia Disorder that is linked to the sex chromosomes Missing a protein needed for the blood to clot

Tay-Sachs Disease Inability to synthesize an enzyme that prevent lipid buildup in brain cells. Causes the breakdown of nervous system

Phenylketonuria (PKU) Inability to code for an enzyme needed for changing the amino acid phenylalanine to tyrosine. Damages brain cells and causes mental retardation.

Duchenne Muscular Dystrophy Linked to the sex chromosomes Results in the progressive weakening and loss of skeletal muscle.

Colorblindness Carried on the X of the sex chromosomes. Occurs more frequently in males than females.

KEY POINT #2 Mutation of a gene = Mutant protein Dysfunctional proteins cause the symptoms of the disorder