Human Genetics

1
Chapter 12

• Human Genetics

2
Ch 12 Overview

• Karyotype- preparation of metaphase chromosomes
  at metaphase they are most condensed and easily
  identified along equator
• Spectral karyotyping
• uses artificial colors for
• diagnostic purposes
• Useful in tracking the
• Phildelphia chromosome,
• first to be linked to
• cancer

3
Ch 12 (overview cont.)

• During stem cell formation, a piece of ? 9 and ?
  22 breaks off
• 22 is shorter, and its broken piece combines
  with 9 (plays a role in cell division) to make an
  abnormally long ? 9 (see below)
• In mutant form, 9 is expressed far more,
  resulting in uncontrolled division of WBC.
• Right Defective Xs 9 and 22 that are linked to
• Chronic myelogenous leukemia (CLM)
• Gleevec is a new drug that stops the cell
• proliferation. So far 5053 patients are in
  remission
• and side effects are mild compared to chemotherapy

4
12.1 Chromosomes and Inheritance

• Homologous chromosomes
• Sister Chromatids
• Gene
• Locus
• Allele (wild-type, mutant)
• Crossing Over
• Genetic recombination
• Independent Assortment
• Know these terms (define and include where/when
  it occurs or is found)

5
12.1 (cont.)

• Exception to homologous chromosomes being
  similar?
• SEX CHROMOSOMES (x and y) (see below right)
• Mammals and fruit flies have XX for female
  diploid cell, XY for male
• Butterflies, moths, some birds and fishes have
  identical sex chromosomes in MALES and
  non-identical in females
• Left Comparing x and y chromosomes
  (some regions are similar, others are not)
  in humans and fruit flies

6
12.1 (cont.)

• Regardless of NOT being homologous, sex
  chromosomes are still able to synapse (zipper
  together briefly) and still function as homologs
  during meiosis
• All other chromosomes
• are autosomes (22 other
• homologous chromosomes
• in diploid body cells)

7
12.2 Karyotyping procedure

• 1. Sample of cells is added to blood
• 2. Colchine is added to arrest mitosis at
  metaphase
• 3. Centrifuge separates cells based on density
• 4. Extract metaphase cells and dilute with saline
  solution
• 5. Prepare slide and stain cells
• 6. Photograph chromosomes, cut out and create
  karyotype

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12.3 Sex Determination in Humans

• Every egg carries an X chromosome (see 2 diagrams
  below)
• ½ the sperm created carry an X, ½ carry a Y
• Y carries only 330 genes, one of which codes for
  the formation of testes
• (which secretes hormones that
• influence development of sexual traits)
• Right and Middle 50
• chance of male vs. female
• Far right sex and non-
• sex related genes on y
• chromosome

9
12.3 (cont.)

• X chromosome has 2062 genes
• Most genes deal with nonsexual traits
  (blood-clotting, color-blindness)
• One gene on X chromosome codes for the production
  of ovaries, which is where egg gametes are
  produced and estrogen is secreted
• Master gene for males is SRY (Sex-determining
  Region of Y-chromosome)
• The SRY encodes for certain proteins
• that regulate many male sex traits, including
• the testes, which secretes testosterone

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12.4 Crossovers and recombinations

• Sex-linked genes- obviously phenotypic results
  that are observed because of gene on x or y
  chromosome
• Color-blindness
• Eye color in fruit flies
• Blood clotting (hemophilia)
• Thomas Morgan discovered that eye color in fruit
  flies is carried on the x chromosome by doing a
  reciprocal cross
• Random mutation resulting in recessive white eyed
  male XrY crossed with a dominant red-eyed female
  XRXR
• (Be sure to review this reciprocal cross on pg.
  200)

11
12.4 (cont.)
12
12.4 (cont.)

• Some alleles are closer together on same
  chromosome and are less likely to undergo
  crossing over
• The probability that a crossover will disrupt
  linkage is proportional to distance that
  separates 2 loci
• Right Genes A and B are more
• likely to be found together after
• recombination has occurred
• compared to A and D
• Hemophilia and color-blindness genes are both
  found on X chromosome in close proximity with
  each other

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12.4 (cont.)

• First linkage map was created in 1990s
• Map conducted by
• tracking phenotypes
• through generations
• Also found that meiosis
• rarely occurs unless every
• pair of homologs undergoes
• at least one crossover
• Right Only child number 3
• received allele M which
• indicates the father's genetic
• material recombined without Hungtingtons Disease
  (HD) gene.

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12.5 Human Genetic Analysis

• Pedigree- chart of genetic connections among
  individuals
• Extrapolations can be made about genetic
  disorders
• dominant or recessive
• Autosomal or sex-linked
• Able to predict probabilities for phenotypic
  outcome for children
• Right pedigree for alkapatonuria,
• autosomal dominant disorder where
• urine turns black due to oxidation of
• Acid in urea

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12.5 (cont.)

• Genetic abnormality is a rare or uncommon version
  of trait (6 toes vs. 5 toes)
• Genetic Disorder is an inherited condition that
  will cause mild to severe medical problems
• Syndrome is a recognized set of symptoms that
  characterize a disorder
• Why dont alleles causing genetic disorders
  disappear entirely from our gene pool?
• Mutations
• Recessive allele can be covered by dominant,
  creating a carrier
• A genetic disease can be a disorder if certain
  factors (nutirition, infection) disrupts body
  functions

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12.6 Examples of Inheritance Patterns

• Galactosemia
• Does not produce enzyme that prevents toxic
  build-up of product from lactose breaking down
• Autosomal recessive (aa)
• Right Glactosidase is present,
• but third enzyme in pathway is
• missing, resulting in build up of galactose
• Galactose levels rise in blood, causing
  malnutrition, diarrhea, vomiting and damage to
  liver, eyes and brain
• If untreated, results in death
• Placed on restrictive diet early enough, grow up
  symptom free

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12.6 (cont.)

• Huntington Disease
• Involuntary movements and deterioration of
  nervous system
• Symptoms may not show up till later (most people
  have reproduced by then)
• Autosomal dominant (Hh or HH)

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12.6 (cont.)

• Achondroplasia (Dwarfism)
• Usually homozygous dominant condition leads to
  still-birth
• Adults less than 4 ft. 4 in. due to improper
  formation of cartilage with skeleton
• Heterozygotes are able to reproduce
• Affects 1/10,000 people

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12.6 (cont.)

• Color-blindness
• X-linked recessive trait (XcXc or XcY)
• Red-green color blindness, individual lacks
  receptors that normally respond to red and green
  wavelengths of light
• Above Which child is colorblind, if any?
  Test for red-green color blindness

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12.6 (cont.)

• Hemophilia A
• Clotting of blood requires several genes, one of
  them being on X chromosome (see probabilities
  below)
• 1/7000 males has the mutated gene on their single
  X chromosome
• Clotting time is close to normal for heterozygous
  females
• Relatives often married
• in 19th century Europe
• Queen Victoria of
• England was a carrier
• (18 of her 69 descendants
• had the recessive allele)

Above right Internal bleeding associated with
Hemophilia
21
12.6 (cont.)

• Fragile X Syndrome
• Causes mental retardation
• in 1/1500 males
• In cultured cells, the X chromosome
• in males is constricted near end of long
• arm called a fragile site, tending
• to break away

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12.6 (cont.)

• A mutant gene actually causes the syndrome in
  body cells
• The mutation codes for repeat units (expansion
  mutation) (CGG)
• This mutation does
• not code for the
• normal protein
• required for brain
• cell development
• An expansion
• mutation is also
• responsible for
• Huntington disease

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12.7 Progeria

• Hutchinson-Gilford Progeria syndrome
• Accelerated aging, greatly reduced life span
• Gene undergoes random, spontaneous mutation
• Symptoms start before age 2
• Skeletal muscles, skin and
• tissue thin and weaken
• Hair loss pronounced
• Usually die in early teens from
• stroke or heart attack

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12.8 Changes in Chromosome Structure

• Four possible mutations, (or structural changes
  in chromosome)
• 1. Duplication. Gene sequences repeated several
  to hundreds of times (see below right)
• 2. Inversion. Stretch of DNA becomes oriented in
  reverse direction (see below left)

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12.8 (cont.)

• 3. Translocation. Broken part of
• chromosome attaches to non-homologous
• chromosome ie) Philadelphia X most are
• reciprocal (both X exchange parts)
• 4. Deletion. Loss of segment of X
• (caused by viral attacks, irradiation,
• chemicals etc.) most deletions are lethal

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12.8 (cont.)

• Cri-du-chat disorder result of chromosome
  deletion
• Irregular shaped larynx, producing a cats meow
  cry in infants
• Deletion of gene on X 5
• Left 1/50,000 people infected normal
  life expectancy but symptoms include low
  birth weights and respiratory problems
  80 of cases, the deletion came from
  chromosome 5 in sperm

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12.8 (cont.)

• Mutations are crucial for evolutionary change
• A duplication in one gene ? a new protein ? codes
  for a structural change in hemoglobin ? produces
  different efficiencies for hemoglobin in carrying
  oxygen
• Of 23 pairs of homologs in humans, 18 are nearly
  identical in chimps and gorillas
• The other 5 pairs differ at inverted and
  translocated regions
• Left Gorilla
• tibia
• Right Human
• tibia

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12.9 Changes in Chromosome

• Aneuploidy. Individuals have one more or less Xs
  as a consequence of abnormalities in meiosis
• ½ all fertilized eggs are aneuploidy, resulting
  in miscarriages and infertility
• Polyploidy. Individuals have 3 or more of each
  type of X
• ½ all plants are polyploidy
• Right Polyploid plants often exhibit
• phenotypes that are a blend of multiple genes
• All but 1 of human polyploids
• die before birth, newborns die
• soon after birth

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12.9 (cont.)

• Nondisjunction-Xs fail to separate during either
  meiosis or mitosis
• Chromosome duplicate during mitosis and stop
  before cytokinesis (tetraploid cells)
• During fertilization,
• new individuals can
• result with one more
• or less chromosome
• trisomic (2n 1) or
• monosomic (2n-1)

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12.9 (cont.)

• Down Syndrome
• Autosomal dominant disorder
• Trisomal (extra chromosome 21)
• 1/900 births
• Nondisjunction during meiosis accounts for 95
  of cases
• Translocation and mosaicism account for 5
• Mosaicism. Nondisjunction occurs after
  fertilization and descendants of that altered
  cell will inherit 3 chromosomes

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12.9 (cont.)

• Nondisjuntion occurs more frequently with
• advancing age of mother
• Symptoms include
• Children may have heart defects and resp.
  problems
• Deep creases across palms and feet
• Flattened facial features
• Life expectancy (avg.) 55 yrs
• Poor muscle tone
• Upward slanted eyes
• Adults often have Alzheimers
• Right Where does in meiosis does
• nondisjunction occur?

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12.10

• Nondisjunction also occurs in X and Y chromosomes
• Leads to difficulties in learning and motor
  functions (often goes undiagnosed)
• Turner Syndrome
• 75 of cases because of nondisjunction in sperm
• XO genotype (only occurs in women)
• 98 of all XO zygotes abort
• 4 8 tall, relatively normal childhood
• Do not have functional ovaries
• Right Karyotype for Turners Syndrome

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12.10 (cont.)

• XXX syndrome. (1/1000 females)
• Except for slight learning difficulties, tend to
  live normal lives, able to reproduce and socially
  interact
• Most females are an inch or so taller and more
  slender
• Klinefelter Syndrome. (1/500, 2000 males)
• Low fertility, but hormone injections can
  reverse feminine traits
• Nondisjunction creates XXY or even XXXY etc.
• Low levels of testosterone, high levels of
  estrogen
• Tend to be taller and overweight, but lead
• relatively normal lives (person with syndrome,
  right)

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12.10 (cont.)

• XYY condition (1/500, 1000 males)
• Taller than average and show mild mental
  impairment
• Once thought to be predisposed to be criminals
• This was hypothesized by doing Double-blind
  Studies
• Two investigators compiled info on karyotypes and
  personal histories independently, THEN combined
  their data to make a false conclusion
• Right XYY karyotype
• In 1976, Danish geneticist gathered accurate
  data XYY males who DO become criminals are
  simply more likely to get caught