Genetic DisordersGenetic Disorders

AP BiologyAP Biology

Detecting Genetic DisordersDetecting Genetic Disorders

AmniocentesisAmniocentesis Chorionic villus samplingChorionic villus sampling KaryotypeKaryotype Sequential Screen (Quad/Triple Sequential Screen (Quad/Triple

Screen)Screen) Blood TestBlood Test

AmniocentesisAmniocentesis A technique for A technique for determining genetic abnormalities in determining genetic abnormalities in a fetus by the presence of certain a fetus by the presence of certain chemicals or defective fetal cells in chemicals or defective fetal cells in the amniotic fluid, obtained by the amniotic fluid, obtained by aspiration from a needle inserted into aspiration from a needle inserted into the uterus.the uterus.

CVS –sample of embryonic cells CVS –sample of embryonic cells taken for chorionic villus taken for chorionic villus (placenta) can be done earlier (placenta) can be done earlier than amniocentesis and results than amniocentesis and results yielded sooneryielded sooner

KaryotypeKaryotype

A method of A method of organizing the organizing the chromosomes chromosomes of of a cell in relation a cell in relation to number, size, to number, size, and type. Taken and type. Taken during during METAPHASE of METAPHASE of Mitosis.Mitosis.

KaryotypeKaryotype

Normal MaleNormal Male

Normal FemaleNormal Female

NON-DISJUNCTIONNON-DISJUNCTION Chromosomes fail to Chromosomes fail to

separate properly - can separate properly - can occur during meiosis I (all occur during meiosis I (all cells affected) or meiosis II cells affected) or meiosis II (half cells affected)(half cells affected)

AneuploidyAneuploidy - having an - having an abnormal chromosome abnormal chromosome numbernumber

Trisomic/TRISOMYTrisomic/TRISOMY - having 3 - having 3 chromosomes 2n+1chromosomes 2n+1

MonosomicMonosomic - having 1 - having 1 chromosome 2n-1chromosome 2n-1

Polyploidy - Polyploidy - having move having move than 2 sets of chromosomesthan 2 sets of chromosomes Triploidy - (3n)Triploidy - (3n) Tetraploidy - (4n) common in Tetraploidy - (4n) common in

plants – usually lethal in plants – usually lethal in animals and humansanimals and humans

Nondisjunction DisordersNondisjunction Disorders

Down’s Syndrome - Trisomy 21Down’s Syndrome - Trisomy 21 Edward’s Syndrome - Trisomy 18Edward’s Syndrome - Trisomy 18 Patau’s Syndrome - Trisomy 13Patau’s Syndrome - Trisomy 13 Turner’s Syndrome - X0Turner’s Syndrome - X0 Klinefelter’s Syndrome - XXYKlinefelter’s Syndrome - XXY Super Male - XYYSuper Male - XYY Super Female - XXXSuper Female - XXX

Down’s SyndromeDown’s Syndrome

Characteristic facial features, low mental ability, stocky build, sometimes heart defects.

Extra copy of chromosome #21 –Trisomy 21

Edward’s SyndromeEdward’s Syndrome

Trisomy 18Trisomy 18 Motor and mental retardationMotor and mental retardation Congenital heart diseaseCongenital heart disease Often dies in infancyOften dies in infancy

Patau’s SyndromePatau’s Syndrome

Trisomy 13Trisomy 13 Physical abnormalities – cleft palate, Physical abnormalities – cleft palate,

polydactaly, microcephalypolydactaly, microcephaly

Turner SyndromeTurner Syndrome

• XO

•Female missing one X chromosome

• short stature

• wide neck with extra skin folds

• underdevelopment of sex characteristics – may lead to sterility

• non-disjunction of sex chromosomes

Klinefelter’s Syndrome XXYKlinefelter’s Syndrome XXY

• XXY

• male with extra X chromosome

•poor sexual development, may be sterile

• subnormal mental ability

• other forms are XXYY, XXXY, XXXXY (additional X’s increase the severity of phenotypes and mental retardation)

Super MaleSuper Male

XYY Jacob’s SyndromeXYY Jacob’s Syndrome Male with extra Y chromosomeMale with extra Y chromosome Very tall, can show violent behaviorVery tall, can show violent behavior Prone to acneProne to acne Impaired fertilityImpaired fertility Mentally normalMentally normal

Chromosomal AbnormalitiesChromosomal Abnormalities

Short Arm of # 5Short Arm of # 5

Cri – du- chat Cri – du- chat Cat-like cryCat-like cry Severe physical Severe physical

and mental and mental abnormalitiesabnormalities

nonlethalnonlethal

Gene MutationsGene Mutations

Point mutationsPoint mutations Changes in 1 or a few Changes in 1 or a few

base pairs in a single base pairs in a single genegene

SubstitutionsSubstitutions

Base-pair Base-pair insertions or insertions or deletionsdeletions: - Can result in : - Can result in a a frameshift mutationframeshift mutation alters the ‘reading frame’ alters the ‘reading frame’ of tripletsof triplets

THE FAT CAT ATE …THE FAT CAT ATE … THF ATC ATA TE….THF ATC ATA TE….

Gene AbnormalitiesGene Abnormalities PointPoint SubstitutionSubstitution

Silent – no change in aaSilent – no change in aaNonsense – STOP CODONNonsense – STOP CODONMissense – change in aaMissense – change in aaTHE FAT CAT ATE THE RAT THE FAT CAT ATE THE RAT T TOOE FAT CAT ATE THE RAT E FAT CAT ATE THE RAT

*Insertion/Addition*Insertion/Addition *Deletion*Deletion*May result in a Frame-Shift Mutation*May result in a Frame-Shift MutationTHTHEE FAT CAT ATE THE RAT FAT CAT ATE THE RAT THF ATC ATA TET HER AT THF ATC ATA TET HER AT

(ENTIRE MESSAGE (ENTIRE MESSAGE SHIFTS)SHIFTS)

TransposonsTransposons (jumping genes) – transfer of a gene from one (jumping genes) – transfer of a gene from one locus to another on a chromosome – may unactivated locus to another on a chromosome – may unactivated relocated gene – which may produce a point mutation and relocated gene – which may produce a point mutation and could result in the elimination of a vital metabolic pathwaycould result in the elimination of a vital metabolic pathway

Sickle Cell AnemiaSickle Cell Anemia

Abnormal Abnormal hemoglobinhemoglobin

1 aa substitution 1 aa substitution causes abnormality causes abnormality (point mutation)(point mutation)

Codominance Codominance (carrier)(carrier) Low oxygen RBC will Low oxygen RBC will

become crescent become crescent shapeshape

Inherited Genetic DisordersInherited Genetic Disorders

Autosomal DominantAutosomal Dominant Inherit one alleleInherit one allele

Autosomal RecessiveAutosomal Recessive Must inherit two recessive alleles, one from Must inherit two recessive alleles, one from

each parent. Parent’s are usually CARRIERS of each parent. Parent’s are usually CARRIERS of the disorderthe disorder

Sex-Linked DisordersSex-Linked Disorders Usually recessive, inherited on X-chromosomeUsually recessive, inherited on X-chromosome More common in males More common in males

Autosomal DominantAutosomal Dominant

Huntington’s DiseaseHuntington’s Disease Marfan SyndromeMarfan Syndrome AchondroplasiaAchondroplasia

Huntington’s Disease Huntington’s Disease Autosomal Dominant Disorder Autosomal Dominant Disorder

(lethal)(lethal) CNS problemCNS problem DementiaDementia Impaired memoryImpaired memory Asymptomatic untilAsymptomatic until

later in lifelater in life (40) (40)

Marfan SyndromeMarfan Syndrome

Autosomal DominantAutosomal Dominant Connective tissue defectConnective tissue defect Tall, thin, long arms and legsTall, thin, long arms and legs Enlarged aortaEnlarged aorta Abe Lincoln did NOT have Abe Lincoln did NOT have

Marfan SyndromeMarfan Syndrome

AchondroplasiaAchondroplasia

Autosomal DominantAutosomal Dominant Defects in growth of long bonesDefects in growth of long bones Form of dwarfismForm of dwarfism Short arms and legs but torso of Short arms and legs but torso of

normal size, large head compared to normal size, large head compared to bodybody

Autosomal RecessiveAutosomal Recessive

PKUPKU AlbinismAlbinism Tay SachsTay Sachs Cystic FibrosisCystic Fibrosis

PKUPKU PhenylketonuriaPhenylketonuria Autosomal Autosomal

RecessiveRecessive Lack enzyme to Lack enzyme to

convert phenylalanine convert phenylalanine to tyrosineto tyrosine

Buildup of Buildup of phenylalanine can phenylalanine can cause retardationcause retardation

Test babies at birthTest babies at birth Special diet for Special diet for

phenylketonuricsphenylketonurics

AlbinismAlbinism

• Lack of pigmentation in skin, hair, eyes

• Inability to make melanin

• Autosomal recessive

Tay-SachsTay-Sachs

Autosomal recessiveAutosomal recessive Degeneration of nervous Degeneration of nervous

systemsystem No enzyme to break down No enzyme to break down

lipids in brain cells, so they lipids in brain cells, so they swell and die (death by age swell and die (death by age 5) - Lethal5) - Lethal

High incidence in Ashkenazie High incidence in Ashkenazie JewsJews

Blood test available to Blood test available to potential parents potential parents

Cystic FibrosisCystic Fibrosis Cystic FibrosisCystic Fibrosis, incurable , incurable

hereditary disorder that causes hereditary disorder that causes the body to secrete an the body to secrete an abnormally thick, sticky mucus abnormally thick, sticky mucus that clogs the that clogs the pancreaspancreas and the and the lungslungs, leading to problems with , leading to problems with breathing and digestion, breathing and digestion, infection, and ultimately, death. infection, and ultimately, death.

Common among CaucasiansCommon among Caucasians One of the most common fatal One of the most common fatal

genetic disordersgenetic disorders in the United in the United StatesStates

LethalLethal Autosomal recessive, caused by Autosomal recessive, caused by

missing 3 bases/1 aa missing 3 bases/1 aa (phenylalanine) protein does not (phenylalanine) protein does not fold correctlyfold correctly

Sex-Linked TraitsSex-Linked Traits

Gene loci on a sex-linked chromosomeGene loci on a sex-linked chromosome Genes for many sex-linked traits, Genes for many sex-linked traits,

unrelated to gender, are found on the X unrelated to gender, are found on the X chromosomechromosome

Follow Mendelian Laws of InheritanceFollow Mendelian Laws of Inheritance May be either dominant or recessiveMay be either dominant or recessive

HemophiliaHemophilia Duchenne Muscular DystrophyDuchenne Muscular Dystrophy ColorblindnessColorblindness

HemophiliaHemophilia

Sex-linked recessive disorderSex-linked recessive disorder Lack of protein necessary for normal blood Lack of protein necessary for normal blood

clottingclotting

Duchenne Muscular Duchenne Muscular DystrophyDystrophy

Sex-linked recessive disorderSex-linked recessive disorder Absence of muscle protein Absence of muscle protein dystrophindystrophin Progressive muscle deterioration and loss Progressive muscle deterioration and loss

of coordination – most die by age of 20of coordination – most die by age of 20

ColorblindnessColorblindness