Chromosomes and human inheritance

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Chromosomes and human inheritance
Genes are distributed in chromosomes. Each gene
has a specific position (locus) on
a chromosome. Each pair of homologous
chromosomes has the same arrangement of genes.
Genes on the same chromosome are linked. The
genes may be identical or different. Variant
forms of genes are called alleles.
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Alleles form through mutation (changes in the DNA
sequence) There may be many different alleles
within the human population, but each
individual will have only two. Combinations of
alleles can be beneficial, have no particular
effect, or contribute to disease
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Humans have tens of thousands of genes arranged
on 46 chromosomes 22 pairs of autosomes
(homologous pairs) 1 pair of sex chromosomes X
and Y are NOT homologous Genes located on sex
(X or Y) chromosomes are called sex- (or X or
Y)-linked genes
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The sex of an individual is determined by
the sperm Female gametes- X or X Male gametes-
X or Y
X X
XX XX
X
XY XY
Y
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The Y chromosome is much smaller than the X
chromosome. For many years it was thought that
there were no genes on the Y chromosome.
It is now known that there are several genes on
the Y chromosome, that contribute to male sexual
development.
There are thousands of genes on the X
chromosome. Do females get a double dose of
these genes?
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No- because of X inactivation In each cell in a
female, one of the X chromosomes is condensed
into a Barr body.
nucleus
Barr body
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What happens if a zygote is formed with the wrong
number of chromosomes? Aneuploidy- too many or
too few chromosomes Polyploidy- three or more
sets of chromosomes Triploidy- three sets of
chromosomes fairly common- 15-18 of
miscarriages A few are born alive- most die
within a month Usually occurs when one egg is
fertilized by two sperm (75 of triploids) In
contrast, polyploid plants are common
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Triploid infant
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How does aneuploidy happen? addition or deletion
of an individual chromosome This usually
happens through nondisjunction (a chromosome pair
fails to separate during meiosis)
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n1
n-1
n
n
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When an aneuploid gamete fuses with a
normal gamete, the offspring will be
aneuploid. When this happens with an autosome
the condition is usually lethal. About 50 of all
abnormalities in fetal death involve
trisomies. A few survive.
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Trisomy 13 Patau syndrome most survive fewer
than 6 months defects in face, eyes, feet,
nervous system and heart More common if
maternal age is higher (over 32). Also
contributes to Trisomy 18 Edwards
syndrome babies are very small, grow
slowly, usually female, and die within 2-4
months due to heart or respiratory
failure Diagnosis by karyotyping
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Trisomy 13 (Patau syndrome) Cleft palate, eye and
neurological problems Average survival 6 months
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Edwards syndrome Malformed hands and feet, heart
defects Life expectancy 4 months Maternal age is
a factor
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Trisomy 21 (Down syndrome) occurs in about 1900
live births characteristic physical
features growth and mental development are
usually retarded approximately 40 of all
people with this syndrome have heart
defects later in life, have very high incidence
of leukemia and/or Alzheimers disease few
live past age 50
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Down syndrome (trisomy 21)
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Maternal age is a risk factor for trisomy 12000
births at age 20 1100 at age 35 130 at age
45 Amniocentesis or CVS (chorionic villus
sampling) recommended for this reason
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• Aneuploidy of sex chromosomes
• more common (1400 in males, 1650
• in females
• Turner syndrome (XO)
• About 110,000 live births
• females lack an X chromosome
• short, broad-chested, do not undergo
• secondary sexual development
• infertile
• not associated with mental retardation

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II. Klinefelter syndrome (XXY) about 11000 live
births not apparent until puberty immature
sexual development- occasion- ally breast
development infertile may have mild
retardation advanced maternal age increases
risk affected male may have several X
chromosomes- the more chromosomes, the more
severe the effect
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III. XYY syndrome about 11000 live
births affected men tend to be unusually
tall MAY have personality disorders or low
intelligence (most dont) Once thought to make
men predisposed to criminal behavior (frequency
of XYY men is unusually high in prisons and
mental institution). No causal relationship
has been proven, though
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Conclusions At least one X chromosome is
required for survival (OY is lethal) Extra X
chromosomes seem to interfere with normal
development (even though all but one is
inactivated in cells) The more X chromosomes are
present, the more severe the effect
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Chromosomes can also be structurally
altered common (1400 frequency) Deletions-
part of chromosome missing Translocation- part
of one chromosome joined to another associated
with a hereditary form of Down syndrome, some
cancers Duplications- part of chromosome is
duplicated effects vary
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Recombination portions of chromosomes are
rearranged
Genes are moved out of position inversions
(ABCD?ACBD) duplications (ABCD?ABBCD) transloc
ations (ABCDEF??ABCJKL (GHIJKL?GHIDEF)
?
?
Effects can be drastic (and permanent)
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What kind of cell is affected and what Are the
consequences?
Germ-line cell (gamete) these mutations are
inherited these give rise to alleles
Somatic cell these affect the particular
tissue but cannot be inherited example tumors
Implications for gene therapy
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Mutations- changes in gene sequence damage error
s in copying gene sequence Cells have mechanisms
to repair this damage but they are not always
completely successful These changes lead to
alleles Sometimes they are harmless, sometimes
they lead to disease (p. 178)
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How do mutations happen?
Spontaneous errors of replication
Chemicals (mutagens, see p. 206)
Radiation
Viruses
If damage to DNA is not repaired, the
mutation becomes incorporated into the genome.
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Genetic disorders Most are recessive (can be
passed from two healthy, carrier parents to a
child) Some alleles are more common than
others some are more common in certain
ethnic groups than others Sickle cell allele-
African descent Cystic fibrosis- European
descent Many of these alleles can now be
identified through testing
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Genetic counseling What contributes to a
high-risk pregnancy? Disease-causing
alleles dominant or recessive alleles- relative
risk of each? Maternal age (Paternal age not
clear)