The Chromosomal Basis of Inheritance

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Chapter 15

• The Chromosomal Basis of Inheritance

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The Chromosomal Theory of Inheritance, 1902

• Walter Sutton, Theodor Boveri, and others
• Mendelian factors are located on chromosomes, it
  is the chromosomes that segregate and assort
  independently

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Evidence of Mendels Factors

• Drosophila melanogaster
• Thomas Hunt Morgan
• tracing a gene to a specific chromosome

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Drosophila experiment

• P white-eyed x red-eyed male female
• F1 all red
• F2 3 red 1 white

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Drosophila experiment, cont.

• maybe females cannot get white eyes
• perform testcross
• white-eyed x hybrid red-eyed
• male female

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Drosophila experiment, cont.

• Eye color
• wild type red (w), dom
• mutant type white (w)
• ? red (w)
• white (w)
• ? red (w w , w w)
• white (w w)
• factors are located on sex chromosomes

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Linked Genes

• genes located on the same chromosome
• complete linkage
• incomplete linkage
• tend to be inherited together
• do not assort independently
• will not produce expected results (ex. 9331)

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Linked Genes, cont.

• completely linked genes
• offspring express only parental types
• incompletely linked genes
• offspring express mostly parental types

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Unlinked Genes

• genes located on different chromosomes
• assort independently
• will produce expected results (ex. 9331)

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Linked and Unlinked Genes

• A AD completely
• D C linked
• AB incompletely
• linked
• B AC unlinked

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Crossing Over

• A.H Sturtevant
• c-o between 2 genes is directly proportional to
  the distance between them
• c-o is more likely to occur between genes that
  are far apart than those close together

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Crossing Over, cont.

• Centimorgans map units
• distance between genes
• used to construct genetic maps

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Human Genetics

• Two procedures for fetal testing
• amniocentesis
• chorionic villi sampling

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Amniocentesis Chorionic villi sampling

• 14-16 weeks
• several weeks for karyotype
• through belly
• more risk

• 8-10 weeks
• 24 hours for karyotype
• through cervix
• less risk

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Human Genome

• normal 46 (23 pairs)
• autosomes 44 (22 pairs)
• sex chromosomes 2
• ? XY - heterogametic sex
• - hemizygous
• ? XX - homogametic sex

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Aneuploidy

• a chromosomal aberration
• monosomic -
• missing one chromosome
• trisomic -
• extra chromosome

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Monosomics

• lost one autosome lethal
• lost one sex chromosome survive (XO)

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Trisomics

• extra autosome
• 13, 15, 18, 21, or 22
• extra sex chromosome
• XXY, XYY, XXX

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Autosomic Aneuploidies
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Down Syndrome

• J. Langdon Down (1866)
• physical characteristics
• epicanthal eye fold
• simian crease on palm
• single crease on little finger
• wide nasal bridge
• large protruding tongue

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Incidence of Down Syndrome

• Incidence 1/750
• incidence increases with increasing maternal age
  (no other disorder is known to follow this
  pattern)

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Down Syndrome Types

• 3 types
• 92 trisomy 21
• 4 translocation
• 2-4 mosaic trisomy 21

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Trisomy 21

• three copies of 21st

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Translocation

• 21st joined to another chromosome
• translocation 14/21
• translocation 21/21

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Mosaic Trisomy 21

• milder form
• believed that fetus contains 47 chromosomes but
  loses one in some cells

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21st Chromosome

• Proto-oncogene
• leukemia rates higher
• Alzheimers disease gene
• Lou Gehrigs disease

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Cause of Down Syndrome

• Nondisjunction
• failure of chromosomes to separate properly in
  meiosis (gametogenesis) or mitosis

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Hypotheses

• 1. Long lag time between meiotic divisions
• 2. Older females are more likely to carry
  embryos with chromosomal anomalies to term than
  younger females

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Sex Chromosomal Aneuploidies
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Y Chromosome

• few genes
• hairy pinna
• webbed toes
• Sry gene
• sex-determining gene

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X Chromosome

• genes
• Duchennes MD
• colorblindness
• hemophilia (royal)

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Lyon Hypothesis

• Mary R. Lyon (1961)
• inactivation of an X chromosome in female mammals
  (random)
• as seen in
• coloration in calico cats

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Barr Bodies

• Murray Barr (1949)
• chromatin (inactive X) appears as a dense object
  in the nucleus
• XX with one Barr body
• XY chromatin negative (no Barr
  body)

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XX Nondisjunctionspermatogenesis and oogenesis

• XXX
• XXY
• YO
• XO

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XXX

• metafemale, trisomy X
• 1/500 female births
• limited fertility
• usually normal in other respects

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XXY (XXYY, XXXY, XXXXY, XXXXXY)

• Klinefelter syndrome
• 1/1000 male births
• sterile
• feminine body contours
• high-pitched voice
• diminished mental capacity

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YO

• Inviable
• at least one X needed for survival

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XO

• Turners syndrome, monosomy X
• 1/2500 female births
• sterile
• short stature
• webbed neck and low-set ears
• low-normal mental range

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YY Nondisjunctionspermatogenesis

• XYY
• extra Y
• 1/1000 male births
• fertile
• normal appearance

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Pedigree

• Study of family histories
• can determine
• sex-linked or autosomal
• dominant or recessive
• heterozygous or homozygous
• one gene or polygenic

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trait present trait absentmale
female
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trait present trait absent
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Multiple Alleles

• genes w/ more than 2 alleles
• example of three alleles
• ABO blood groups

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ABO blood groups

• universal donor O -
• universal recipient AB

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Rh factor

• Rh
• Rh 85
• Rh - 15
• erythroblastosis fetalis
• mother Rh -
• father Rh
• baby Rh

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Genetic Disorders

• Not equally distributed among various human
  populations
• some are lethal soon after birth others are
  lethal later in life

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Genetic Disorders list

• Cystic fibrosis (CF),
• Sickle-cell disease,
• Tay-Sachs disease,
• Phenylketonuria (PKU),
• Hemophilia,
• Huntingtons disease,
• Hypercholesterolemia

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Cystic fibrosis (CF)

• rec
• symptom mucous clogging
• defect failure of Cl- transport
• most common fatal genetic disorder among whites

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Sickle-cell disease (homozygous) Sickle-cell
trait (heterozygous)

• codominant (molecular level), heterozygous w/
  normal and abnormal cells
• symptom poor blood circulation
• defect abnormal hemoglobin
• most common inherited disease among Afroamericans

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Tay-Sachs disease

• codominant (molecular level)
• incomplete dom (biochem level)
• rec (organismal level) because individual
  produces some enzyme to prevent cell destruction
• homozygous (two genes)
• juvenile Tay-Sachs
• heterozyggous (one gene)
• late-onset Tay-Sachs

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Tay-Sachs disease, cont.

• symptom deterioration of CNS
• defect defective enzyme
• more common among central European Jews

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Phenylketonuria (PKU)

• rec
• symptom failure of brain cells to develop
• defect absent or defective enzyme
• predominantly individuals with very fair skin

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Hemophilia

• rec (autosomal) and
• sex-linked (royal)
• symptom failure of blood to clot properly
• defect defective blood clotting factor

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Huntingtons disease

• dom
• symptom gradual brain cell deterioration
• defect inhibition of brain cell metabolism

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Hypercholesterolemia

• incomplete dominance
• homozygous, 5X cholesterol
• heterozygous, 2X cholesterol
• symptom excessive cholesterol levels in blood
• defect abnormal number of cholesterol receptors

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Genomic Imprinting

• Identical alleles do not always have the same
  effects on offspring
• depends on which parent passed it along
• example deletion on 15th
• maternalAngelman Syndrome
• paternalPrader-Willi syndrome

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Chapter 14

• END