HUMAN GENETICS What can go wrong? Chromosome Gene Mutations Mutations

Chromosomal Abnormalities 1 infant in 200 newborns has a chromosomal abnormality 28% of first trimester miscarriages have a chromosomal abnormality Abnormalities in larger chromosomes don’t usually survive

MUTATION BENEFICIAL HARMFUL A change in the DNA code of an organism is called a ______________________ Mutations can be _______________ OR ______________ MUTATION BENEFICIAL HARMFUL

BENEFICIAL MUTATIONS Help an organism survive and reproduce Provide variation in population for natural selection to act upon Ex: White fur if you live in a snowy place Image from: http://www.cheryllavender.com/Snow%20Rabbit.jpg

HARMFUL MUTATIONS LETHAL Can result in death =___________ (even before birth) Cause a genetic disorder Cause cancer

SOMATIC CELL MUTATIONS If the change happens in a BODY CELL (lung, liver, brain, muscle, etc.) = ______________________ Somatic cell mutations can: ______________________ ______________________ _____________ Somatic cell mutation Cause cancer Make cell not able to function Kill cell BUT won’t be passed on to offspring

GERM CELL MUTATION Germ cell mutation If the change happens in Gametes (sperm & eggs) = _______________________ Germ cell mutation Can be passed on to offspring

What can go wrong? GENE ___________Mutations- Changes in an individual gene __________________Mutations Changes in the number of chromosomes CHROMOSOME

ADDITION A T T C G A G C T A T T C G T A A G C T Putting in extra bases during copying A T T C G A G C T A T T C G T A A G C T

SUBSTITUTION A T T C G A T T G C T Changes one base for another A T T C G A G C T A T T C G A T T G C T

DELETION Piece of whole chromosome is lost ________________________________________ Image from: http://www.biology-online.org/2/8_mutations.htm

DUPLICATION Piece of DNA is copied too many times ________________________________________________ Image from: http://www.biology-online.org/2/8_mutations.htm

INVERSION Segment flips and reads backwards Image from: http://www.biology-online.org/2/8_mutations.htm

TRANSLOCATION Segment breaks off and joins a different non-homologous chromosome Image from: http://www.biology-online.org/2/8_mutations.htm

DNA RNA PROTEIN   GENE MUTATIONS Changes in the DNA code of a single gene DNA  RNA PROTEIN  ___________ ____________ ______________________

PROTEINS are built from AMINO ACID subunits Image by: Riedell

Each group of 3 nitrogen bases codes for a different amino acid There are 20 different AMINO ACIDS used by cells to make PROTEINS

Proteins are made by joining amino acids together in long chains Image from:  http://www.ust.hk/roundtable/hi-tech.series/1_b1.jpg

Harmful Gene Mutations Point mutations – change a _________ base in DNA code Frame shift mutations change _____________ bases in code SINGLE MULTIPLE

FRAME SHIFT MUTATIONS Caused by changes in code that are NOT multiples of DNA message is read in groups of three nitrogen bases

____________________ DELETION theatcatranandran _____________________ FRAME SHIFT MUTATIONS thefatcatranandran ____________________ DELETION theatcatranandran _____________________ the fat cat ran and ran the atc atr ana ndr an

FRAME SHIFT MUTATIONS at beginning of gene are more damaging than those at end because more of gene is changed thefatcatranandran ____________________ DELETION near front theatcatranandran _____________________ DELETION near end the fat cat ran and ran the atc atr ana ndr an thefatcatranandrn

HUMAN GENETIC DISORDERS Caused by Gene Mutations

DELETION Piece of whole chromosome is lost ________________________________________ Image from: http://www.biology-online.org/2/8_mutations.htm

Cri-du-chat (Cat cry) (5p-) 1 in 50,000 births More common in girls

Mewing cry in infancy Missing piece of number 5 Mental retardation 50% have heart defects

Prader-Willi Syndrome Deletion in chromosome 15 Feeding problems: poor weight gain in infancy, won’t eat Ages 1-6 excessive, rapid weight gain Under developed sex organs Mild to moderate retardation Obsession with food Complications from problems associated with obesity (heart attack, high blood pressure, diabetes)

Prader-Willi syndrome Victor at age 1 Victor at age 2

SUBSTITUTION A T T C T A G C T Changes one base for another A T T C G A G C T A T T C T A G C T

A gene that is flipped and reads backwards will not work. A gene that is moved to another chromosome will not separate from its partner during meiosis. One cell can get 2 copies of gene, one cell gets none.

SICKLE CELL ANEMIA CAUSE: (autosomal recessive) A changed to T (glu to val) gene on chromosome #11 that codes for part of hemoglobin protein (carries oxygen in blood)

SICKLE CELL ANEMIA SYMPTOMS: Sickle shaped Red Blood Cells in hh persons Circulatory problems Loss of blood cells (anemia) Organ damage DEATH

SICKLE CELL ANEMIA More common in African Americans 1 in 500 = hh 1 in 10 = Hh carriers for gene Hh persons have Sickle cell TRAIT make some normal RBC’s’ ; some sickled cells

Having two copies of gene (hh) makes a person sick Having one copy (Hh)- gives person resistance to MALARIA http://www-klinik.uni-mainz.de/Zentrallabor/Lab-Web/Bilder/Malaria_5.jpg

DELETION Piece of DNA code for one gene is lost ________________________________________ Image from: http://www.biology-online.org/2/8_mutations.htm

Duchenne Muscular Dystrophy CAUSE: (X linked recessive) DELETION in gene that codes for a muscle protein

Duchenne Muscular Dystrophy (DMD) SYMPTOMS: 1 in 3500 male births Appears before age 5 Progressive muscle weakening Most in wheelchair by age 13 Eventually lethal

DUPLICATION Piece of DNA is copied too many times ________________________________________________ Image from: http://www.biology-online.org/2/8_mutations.htm

FRAME SHIFT MUTATIONS Changes multiple bases in code thefatcatranandran ____________________ DUPLICATION thefatcatranandandandandran ___________________________ the fat cat ran and ran the fat cat ran and and and ran

HUNTINGTON’S CAUSE: Autosomal dominant 40-100 CAG Repeats at end of gene on chromosome 4

HUNTINGTON’S SYMPTOMS: Seen in both males and females Degenerative brain disorder Symptoms appear age 30-40 (Usually after having children) Lose ability to walk, think, talk, reason 50/50 chance of passing it to child SYMPTOMS: Seen in both males and females

Until now people didn’t know they had the gene, until after they had already had children. Now there is a test to tell if you have the gene before symptoms appear. Would you want to know if there is NO cure?

Genetic disorders can be carried on: AUTOSOMES = ________________ SEX CHROMOSOMES = _______________ AUTOSOMAL SEX-LINKED

OTHER GENETIC DISEASES AUTOSOMAL RECESSIVE Phenylketonuria Cystic fibrosis Albinism X-LINKED RECESSIVE Color blindness Hemophilia Muscular dystrophy AUTOSOMAL DOMINANT Achondroplasia (Dwarfism) Huntington’s

HEMOPHILIA CAUSE: change in gene on X chromosome that codes for blood clotting protein SYMPTOMS: More common in males Internal and external bleeding Can result in death transfusions/hospitalization required frequently to stop bleeding

ACHONDROPLASIA (Dwarfism) CAUSE: (Autosomal Dominant on chromosome 4) Most are new mutations in egg or sperm cell, but it can be inherited from parent with gene 1 in 20,000 births 200,000 “little people” worldwide One of oldest known – seen in Egyptian art Normal size torso; short arms and legs Problem with way cartilage changes to bone as bones grow

COLOR BLINDNESS CAUSE: X linked recessive Mutation in gene on X chromosome SYMPTOMS: More common in males (8% of males are colorblind) Can’t distinguish certain colors Most common = red/green

Cystic Fibrosis Mutation in gene on chromosome 7 that codes for protein in membrane that transports chloride ions

Cystic Fibrosis Autosomal recessive Symptoms: More common in Caucasians Make extra thick mucous in lungs and pancreas which leads to respiratory and digestive complications Salty skin is clue

Phenylketonuria (PKU) CAUSE: Mutation in gene for enzyme that changes the amino acid phenylalanine into tyrosine Build up causes brain damage ALL babies have blood test for PKU when born before leaving hospital Treatment: Diet low in phenylalanine can extend life and prevent retardation * Nutri-sweet warning

All “SUGAR-FREE” foods have a warning label * PHENYLKETONURICS: Contains phenylalanine Image from: http://www.themagicgadget.co.uk/xcart/search.php?mode=search

HUMAN GENETICS What can go wrong? Chromosome Mutations Changes in chromosome number

Missing chromosomes (monosomy) EX: Turner’s syndrome - X0 Changes in chromosome number ____________________________ Missing chromosomes (monosomy) EX: Turner’s syndrome - X0 Extra chromosomes (trisomy) EX: Down’s syndrome – 3 #21’s Kleinfelter’s syndrome- XXy

NON-DISJUNCTION A homologous pair sticks together and doesn’t separate at MEIOSIS. One cell gets 2 copies of the chromosome the other cell gets none.

Normal Meiosis

Nondisjunction

Nondisjunction Chromosomes don’t separate at anaphase Cell gets 2 copies of a chromosome OR none After fertilization new baby gets 3 of each chromosome (trisomy) or only 1 copy of each (monosomy)

Normal division Non-disjunction

Human Abnormalities Caused by Non-Disjunction Down’s syndrome Patau syndrome Kleinfelter syndrome Turner’s syndrome Xyy

Down’s syndrome (trisomy 21)

Down’s syndrome (trisomy 21) 1 in 660 births Similar facial features Slanted eyes Protruding tongue

Down’s syndrome (trisomy 21) Simian line on palm

Down’s syndrome (trisomy 21) Most common chromosomal abnormality 50% have heart defects that need surgery to repair Mental retardation Risk increases with age of mom

Patau syndrome (trisomy 13)

Patau syndrome (trisomy 13) Can be traced back 300 years in literature 1st identified as a chromosomal cause in 1960 1 in 7000 births (rare)

Patau syndrome (trisomy 13) Cleft lip & palate Eye abnormalities (too small or missing)

Patau syndrome (trisomy 13) Low set ears Polydactyly

Turner’s syndrome (monosomy)

Turner’s syndrome XO 1 in 5000 births Female = XO Small size Slightly decreased intelligence 35% have heart abnormalities Hearing loss common Broad chest Undeveloped ovaries/can’t have children

Kleinfelter syndrome Xxy (trisomy)

Kleinfelter syndrome 1 in 1000 births Male = XXy Average to slight decrease in intelligence Small testes/ can’t have children Usually not discovered until puberty when don’t mature like peers

Xyy syndrome Xyy males Taller Average intelligence Some study show increased learning disabilities Most lead normal lives