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PowerLecture:PowerLecture:Chapter 12Chapter 12
Chromosomes and Human Chromosomes and Human InheritanceInheritance
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Genes Genes
Units of information about heritable traitsUnits of information about heritable traits
In eukaryotes, distributed among In eukaryotes, distributed among chromosomeschromosomes
Each has a particular locus Each has a particular locus
Location on a chromosomeLocation on a chromosome
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Homologous ChromosomesHomologous Chromosomes
Homologous autosomes are identical in Homologous autosomes are identical in length, size, shape, and gene sequencelength, size, shape, and gene sequence
Sex chromosomes are nonidentical but still Sex chromosomes are nonidentical but still homologoushomologous
Homologous chromosomes interact, then Homologous chromosomes interact, then segregate from one another during meiosissegregate from one another during meiosis
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AllelesAlleles
Different molecular forms of a geneDifferent molecular forms of a gene
Arise through mutationArise through mutation
Diploid cell has a pair of alleles at each locusDiploid cell has a pair of alleles at each locus
Alleles on homologous chromosomes may be Alleles on homologous chromosomes may be
same or differentsame or different
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Sex ChromosomesSex Chromosomes
Discovered in late 1800sDiscovered in late 1800s
Mammals, fruit fliesMammals, fruit flies
XX is female, XY is maleXX is female, XY is male
In other groups XX is male, XY femaleIn other groups XX is male, XY female
Human X and Y chromosomes function as Human X and Y chromosomes function as
homologues during meiosishomologues during meiosis
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Karyotype Preparation - Karyotype Preparation - Stopping the Cycle Stopping the Cycle
Cultured cells are arrested at metaphase by Cultured cells are arrested at metaphase by adding colchicineadding colchicine
This is when cells are most condensed and This is when cells are most condensed and easiest to identifyeasiest to identify
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Karyotype PreparationKaryotype Preparation
Arrested cells are broken openArrested cells are broken open
Metaphase chromosomes are fixed and Metaphase chromosomes are fixed and stainedstained
Chromosomes are photographed Chromosomes are photographed through microscopethrough microscope
Photograph of chromosomes is cut up Photograph of chromosomes is cut up and arranged to form karyotype diagramand arranged to form karyotype diagram
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Fig. 12-4, p.189
Karyotype Preparation
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Autosomal Autosomal Dominant InheritanceDominant Inheritance
Trait typically Trait typically appears in every appears in every generationgeneration
Fig. 12-10a, p. 190
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AchondroplasiaAchondroplasia
Autosomal dominant Autosomal dominant alleleallele
In homozygous form In homozygous form usually leads to usually leads to stillbirthstillbirth
Heterozygotes Heterozygotes display a type of display a type of dwarfismdwarfism Have short arms and legs relative to
other body parts
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Huntington Huntington DisorderDisorder
Autosomal dominant Autosomal dominant alleleallele
Causes involuntary Causes involuntary movements, nervous movements, nervous system deterioration, system deterioration, deathdeath
Symptoms don’t usually Symptoms don’t usually show up until person is show up until person is past age 30past age 30
People often pass allele People often pass allele on before they know on before they know they have itthey have it
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Autosomal Recessive Autosomal Recessive Inheritance PatternsInheritance Patterns
If parents are both If parents are both heterozygous, child heterozygous, child will have a 25% will have a 25% chance of being chance of being affected affected
Fig. 12-10b, p. 191
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GalactosemiaGalactosemia
Caused by autosomal recessive alleleCaused by autosomal recessive allele
Gene specifies a mutant enzyme in the pathway Gene specifies a mutant enzyme in the pathway that breaks down lactosethat breaks down lactose
galactose-1-phosphate
enzyme 2
lactose galactose
enzyme 1
+glucose
galactose-1-phosphate
enzyme 3
intermediatein glycolysis
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Hutchinson-Gilford ProgeriaHutchinson-Gilford Progeria
Mutation causes Mutation causes
accelerated agingaccelerated aging
No evidence of it running No evidence of it running
in familiesin families
Appears to be dominantAppears to be dominant
Seems to arise as Seems to arise as
spontaneous mutationspontaneous mutation
Usually causes death in Usually causes death in
early teens early teens
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x
x
eggs sperm
diploidgerm cellsin female
diploidgerm cellsin male
meiosis, gameteformation in bothfemale and male:
sex chromosomecombinations
possible in newindividual
Fertilization:
XX XX
X
X
Y
X
XX
X
X XY XY
Fig. 12-8a, p.192
Sex Determination
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The Y ChromosomeThe Y Chromosome
• Fewer than two dozen genes
identified
• One is the master gene for
male sex determination
– SRY gene (sex-determining
region of Y)
• SRY present, testes form
• SRY absent, ovaries form
• NPR
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The X ChromosomeThe X Chromosome
• Carries more than 2,300 genes
• Most genes deal with nonsexual traits
• Genes on X chromosome can be expressed in both males and females
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EmbryologistEmbryologist
DrosophilaDrosophila, fruit fly’s , fruit fly’s X chromosome has X chromosome has the gene for eye color the gene for eye color and another gene for and another gene for body color (p193)body color (p193)
D. melanogasterD. melanogaster
Reciprocal crossesReciprocal crosses
Thomas MorganThomas Morgan
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Fig. 12-9, p.193
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X-Linked Recessive InheritanceX-Linked Recessive Inheritance
Males show disorder Males show disorder more than femalesmore than females
Son cannot inherit Son cannot inherit disorder from his disorder from his fatherfather
Fig. 12-10, p.194
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Examples of X-Linked TraitsExamples of X-Linked Traits
Color blindnessColor blindness
Inability to distinguish among some of all colorsInability to distinguish among some of all colors
HemophiliaHemophilia
Blood-clotting disorderBlood-clotting disorder
1/7,000 males has allele for hemophilia A1/7,000 males has allele for hemophilia A
Was common in European royal familiesWas common in European royal families
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Fig. 12-12, p.195
Color Blindness
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Fig. 12-12, p.195
Color Blindness
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Fig. 12-11, p.194
Hemophilia
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Duchenne Muscular DystrophyDuchenne Muscular Dystrophy
Rapid degeneration of muscles Starts early, 3-7 yo.1 in 3500 boysEncodes dystropin that supports fused together cells in muscle fibers
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Fragile X SyndromeFragile X Syndrome
An X-linked recessive An X-linked recessive
disorderdisorder
Causes mental Causes mental
retardationretardation
Mutant allele for gene Mutant allele for gene
that specifies a protein that specifies a protein
required for brain required for brain
developmentdevelopment
Allele has repeated Allele has repeated
segments of DNAsegments of DNA
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DuplicationDuplication
Gene sequence that Gene sequence that
is repeated several to is repeated several to
hundreds of times hundreds of times
Duplications occur in Duplications occur in
normal chromosomesnormal chromosomes
May have adaptive May have adaptive
advantageadvantage
Useful mutations may Useful mutations may
occur in copyoccur in copy
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DuplicationDuplicationKaryotype of duplicated chromosomes of the Karyotype of duplicated chromosomes of the gibbon.gibbon.
Fig. 12-14, p.197
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DeletionDeletionLoss of some segment of a chromosomeLoss of some segment of a chromosome
Most are lethal or cause serious disorderMost are lethal or cause serious disorder
Common in cancerous cellsCommon in cancerous cells
http://nitro.biosci.arizona.edu/courses/EEB320-2007/Lecture40/lecture40.html
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Cri du ChatCri du Chat
Fig. 12-13, p.196
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InversionInversionA linear stretch of DNA is reversed A linear stretch of DNA is reversed
within the chromosomewithin the chromosome
Paracentric inversion of short arm
Paracentric inverstion of long arm
Paracentric inversion
http://www.tokyo-med.ac.jp/genet/cai-e.htm
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TranslocationTranslocation
A piece of one chromosome becomes attached A piece of one chromosome becomes attached to another nonhomologous chromosometo another nonhomologous chromosome
Most are reciprocalMost are reciprocal
Philadelphia chromosome arose from a Philadelphia chromosome arose from a reciprocal translocation between chromosomes reciprocal translocation between chromosomes 9 and 229 and 22 Reciprocal
translocation
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Chromosome StructureChromosome Structure
Alterations to chromosome structure are Alterations to chromosome structure are usually badusually bad
Duplications are adaptive: one gene functions Duplications are adaptive: one gene functions normally - the other is free to mutatenormally - the other is free to mutate
Chromosome structure evolvesChromosome structure evolves
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Chromosome StructureChromosome Structure
Human body cells have 23 pairs of Human body cells have 23 pairs of chromosomeschromosomes
Chimpanzees, gorilla, or orangutan body cells Chimpanzees, gorilla, or orangutan body cells have twenty-four pairs of chromosomeshave twenty-four pairs of chromosomes
During human evolution, two chromosomes in During human evolution, two chromosomes in an early ancestor fused to form chromosome 2 an early ancestor fused to form chromosome 2 (p197)(p197)
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Fig. 12-15, p.197
chimpanzeehuman gorilla orangutan
Chromosome Chromosome StructureStructure
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AneuploidyAneuploidy
Individuals have one Individuals have one extra or less extra or less chromosome chromosome
(2(2nn + 1 or 2 + 1 or 2nn - 1) - 1)
Major cause of human Major cause of human reproductive failurereproductive failure
Most human Most human miscarriages are miscarriages are aneuploids aneuploids
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PolyploidyPolyploidyIndividuals have three Individuals have three or more of each type of or more of each type of chromosome (3chromosome (3nn, 4, 4nn))
Common in flowering Common in flowering plantsplants
Lethal for humansLethal for humans
99% die before birth99% die before birth
Newborns die soon after Newborns die soon after birthbirth
Easter Lily (4n), where n=12.
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n + 1
n + 1
n - 1
n - 1
chromosome alignments at metaphase I
NONDISJUNCTION AT ANAPHASE I
alignments at metaphase II
anaphase II CHROMOSOMENUMBER INGAMETES
Fig. 12-16b, p.198
Nondisjunction
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Down SyndromeDown SyndromeTrisomy of chromosome Trisomy of chromosome 2121
Mental impairment and a Mental impairment and a variety of additional variety of additional defectsdefects
Can be detected before Can be detected before birthbirth
Risk of Down syndrome Risk of Down syndrome increases dramatically in increases dramatically in mothers over age 35mothers over age 35
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Turner SyndromeTurner Syndrome
Inheritance of only one X Inheritance of only one X (XO)(XO)
98% spontaneously 98% spontaneously abortedaborted
Survivors are short, Survivors are short, infertile femalesinfertile females
No functional ovariesNo functional ovaries
Secondary sexual traits Secondary sexual traits reducedreduced
May be treated with May be treated with hormones, surgeryhormones, surgery
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Klinefelter SyndromeKlinefelter Syndrome
XXY conditionXXY conditionResults mainly from Results mainly from nondisjunction in nondisjunction in mother (67%)mother (67%)Phenotype is tall Phenotype is tall malesmales
Sterile or nearly soSterile or nearly soFeminized traits Feminized traits (sparse facial hair, (sparse facial hair, somewhat enlarged somewhat enlarged breasts)breasts)Treated with Treated with testosterone injectionstestosterone injections
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XYY ConditionXYY Condition
Taller than average Taller than average malesmales
Most otherwise Most otherwise phenotypically normalphenotypically normal
Some mentally Some mentally impairedimpaired
Once thought to be Once thought to be predisposed to predisposed to criminal behavior, but criminal behavior, but studies now discreditstudies now discredit
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Human Genetic AnalysisHuman Genetic Analysis
Unlike lab animals, weUnlike lab animals, weLive under variable conditionsLive under variable conditions
Live long, select our own matesLive long, select our own mates
Reproduce when we want toReproduce when we want to
Small familiesSmall families
Gather information from several generations Gather information from several generations and create pedigreesand create pedigrees
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Pedigree Pedigree Symbols Symbols
male
female
marriage/mating
Individual showing trait being studied
sex not specified
generationI, II, III, IV...
offspring in order of birth, from left to right
Fig. 12-19a, p.200
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Fig. 12-19b,p.200
http://www.eatonhand.com/hw/hw024.htm
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Abnormality vs. DisorderAbnormality vs. Disorder
A rare, uncommon A rare, uncommon
version of a traitversion of a trait
PolydactylyPolydactyly
Unusual number of toes Unusual number of toes
or fingersor fingers
Does not cause any Does not cause any
health problemshealth problems
View of trait as View of trait as
disfiguring is subjectivedisfiguring is subjective
Inherited conditions that Inherited conditions that
cause mild to severe cause mild to severe
medical problemsmedical problems
Why don’t they Why don’t they
disappear?disappear?
Mutation introduces Mutation introduces
new rare allelesnew rare alleles
In heterozygotes, In heterozygotes,
harmful allele is harmful allele is
masked, so it can still masked, so it can still
be passed on to be passed on to
offspring offspring
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Phenotypic TreatmentsPhenotypic Treatments
Symptoms of many genetic disorders can be Symptoms of many genetic disorders can be
minimized or suppressed byminimized or suppressed by
Dietary controlsDietary controls
Adjustments to environmental conditionsAdjustments to environmental conditions
Surgery or hormonal treatmentsSurgery or hormonal treatments
Phenykentonuria (PKU)Phenykentonuria (PKU)
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Genetic ScreeningGenetic Screening
Large-scale screening programs detect Large-scale screening programs detect affected persons affected persons
Newborns in United States routinely tested Newborns in United States routinely tested for PKUfor PKU
Early detection allows dietary intervention and Early detection allows dietary intervention and prevents brain impairmentprevents brain impairment
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Prenatal DiagnosisPrenatal Diagnosis
AmniocentesisAmniocentesis
Chorionic villus samplingChorionic villus sampling
FetoscopyFetoscopy
All methods have some risksAll methods have some risks
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Fig. 12-21, p.202
Image on the ultrasound screen Amniocentesis
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Fig. 12-22, p.202
Fetoscopy
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Preimplantation DiagnosisPreimplantation Diagnosis
Used with in-vitro fertilizationUsed with in-vitro fertilization
Mitotic divisions produce ball of 8 cellsMitotic divisions produce ball of 8 cells
All cells have same genesAll cells have same genes
One of the cells is removed and its genes One of the cells is removed and its genes
analyzedanalyzed
If cell has no defects, the embryo is If cell has no defects, the embryo is
implanted in uterusimplanted in uterus