HUMAN GENETICS

HUMAN GENETICSWhat can go wrong?

Chromosome GeneMutations 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

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

Image from: http://www.cheryllavender.com/Snow%20Rabbit.jpg

HARMFUL MUTATIONS

Can result in death =___________(even before birth)

Cause a genetic disorder

Cause cancer

LETHAL

SOMATIC CELL MUTATIONSIf 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 If the change happens in Gametes

(sperm & eggs)

= _______________________Germ cell mutation Can be passed on to offspring

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-DISJUNCTIONA 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

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

• Lead normal lives

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)


Cleft lip & palate

Eye abnormalities

(too small or missing)


Low set ears

Polydactyly

DELETION________________________________________ Piece of whole chromosome is lost

Image from: http://www.biology-online.org/2/8_mutations.htm

Human Abnormalities Caused by Deletions

• Wolf-Hirschhorn syndrome

• Cri-du-chat syndrome

• Prader-Willi Syndrome

Wolf-Hirschhorn syndrome (4p-)• Missing piece on

short arm of chromosome 4


• Large low set ears

• Club feet

Cri-du-chat (Cat cry) (5p-)

• 1 in 50,000 births• More common in girls

• Mewing cry in infancy

• Missing piece of number 5


• 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

INVERSION

Segment flips and reads backwards


TRANSLOCATIONSegment breaks off and joins a

different non-homologous chromosome


A gene that is flipped and reads backwards will not work.

A gene that is moved toanother chromosome will not separate fromits partner during meiosis.One cell can get 2 copiesof gene, one cell gets none.

GENE MUTATIONS Changes in the DNA code of a single gene

DNA RNA PROTEIN___________ ____________ ______________________

Harmful Gene Mutations1. Point mutations – changes a _________ base in DNA code 1. __________________

2. Frame shift mutationschanges _____________ bases in code

1. ___________________

2. ________________

SINGLE

MULTIPLE

Substitution

Deletion

Addition

SUBSTITUTION

Changes one base for another

A T T C G A G C T

A T T C T A G C T

SICKLE CELL ANEMIACAUSE:

(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 ANEMIASYMPTOMS:Sickle shaped Red Blood Cells in hh persons

Circulatory problemsLoss of blood cells (anemia)Organ damageDEATH

SICKLE CELL ANEMIAMore 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

FRAME SHIFT MUTATIONSChanges multiple bases in code

thefatcatranandran

____________________

DELETION

theatcatranandran

_____________________

the fat cat ran and ran

the atc atr ana ndr an

FRAME SHIFT MUTATIONSat 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 atc atr ana ndr an

thefatcatranandrn

DELETION________________________________________ Piece of DNA code for one gene is lost


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

DUPLICATIONPiece of DNA is copied too many times________________________________________________


FRAME SHIFT MUTATIONSChanges multiple bases in code thefatcatranandran

____________________

DUPLICATION

thefatcatranandandandandran

___________________________


the fat cat ran and and and ran

HUNTINGTON’S

40-100 CAG Repeats at end of gene on chromosome 4

CAUSE: Autosomal dominant

HUNTINGTON’S• 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?

OTHER GENETIC DISEASESAUTOSOMAL RECESSIVE• Phenylketonuria • Cystic fibrosis • Albinism X-LINKED RECESSIVE• Color blindness• Hemophilia• Muscular dystrophyAUTOSOMAL DOMINANT• Achondroplasia (Dwarfism)• Huntington’s

HEMOPHILIACAUSE:

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 births200,000 “little people” worldwideOne of oldest known – seen in Egyptian artNormal size torso; short arms and legsProblem with way cartilage changes to bone as bones grow

COLOR BLINDNESSCAUSE:

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 FibrosisMutation in gene on chromosome 7 that

codes for protein in membrane that transports chloride ions

Cystic FibrosisAutosomal 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” foodshave a warning label

* PHENYLKETONURICS: Contains phenylalanine

Image from: http://www.themagicgadget.co.uk/xcart/search.php?mode=search

http://www.themagicgadget.co.uk/xcart/product.php?productid=445&cat=0&page=1

HUMAN GENETICS

Documents

Transcript of HUMAN GENETICS