Download Errors and Exceptions in Chromosomal Inheritance

Errors and Exceptions in
Chromosomal Inheritance
Errors
• Physical and
chemical
disturbances
• Errors during meiosis
• Plants are more
tolerant of genetic
defects than animals
Nondisjunction
• Occurs when problems
with meiotic spindle
cause errors in daughter
cells
– If tetrad chromosomes fail
to separate properly
during Meiosis I
– Sister chromatids fail to
separate during Meiosis II
• One gamete receives
two copies of the same
chromosome, another
gamete receives no copy
Aneuploidy
• Results when a fertilization
occurs between a normal
gamete and a gamete from
nondisjunction
– Trisomy=have 3 copies of a
particular chromosome (2n+1)
– Monosomy=have only one
copy of a particular
chromosome (2n-1)
• If organisms survives,
aneuploidy typically leads to
a distinct phenotype
Aneuploidy
• Can also occur due to a failure of the
mitotic spindle after fertilization
• If this happens early in development, the
aneupliod condition will be passed to a
large number of cells
– Can have a substantial effect on the organism
Polyploid
• Organisms with more than two complete
sets of chromosome
– Normal gamete fertilizes gamete in which
there has been nondisjunction of all the
chromsomes
• Results in triploid (3n)
– If a 2n zygote fails to divide after replication, a
tetraploid (4n) embryo would result from
future successful cycles of mitosis
Polyploidy
• Common is fairly common among plants
• Much less common among animals
– Is known to occur in fish and amphibians
– Plays an important role in evolution of plants
– Researchers in Chile have identified a new rodent
species that may be a polyploid
• Polyploids are more normal than aneuploids
– One extra missing chromosome apparently
upsets the genetic balance during development
than does an entire extra set of chromosomes
Polyploidy
Polyploidy in humans causes
miscarriage (69, XXY)
Chromosome breakage
• Four types of changes in chromosome
structure as a result of breakage
– Deletion
– Duplication
– Inversion
– translocation
Deletion
• A chromosome
fragment lacking a
centromere is lost
during cell division
• Chromosome will be
missing certain genes
Duplication
• A fragment becomes
attached as an extra
segment to a sister
chromatid
– A detached fragment may
attach to a nonsister
chromatid of a homologous
chromosome
– Duplicated segments will not
be identical if the
homologues carry different
alleles
– Results in multiple copies of
some genes
Inversion
• Chromosomal
fragment reattaches
to the original
chromosome, but in
the reverse
orientation
Translocation
• Chromosomal
fragment joins a
nonhomologous
chromosome
Errors
• Deletions and
duplications are likely to
occur during meiosis
– Homologous chromatids
may break and rejoin at
incorrect places during
crossing over
• One chromosome loses
more genes than it receives
• Products of a nonreciprocal
crossover are one
chromosome with a deletion
and one with a duplication
Large deletions
• A diploid embryo that is homozygous for a large
deletion or a male with a large deletion on its X
chromosome is usually missing many essential
genes
– Usually lethal
• Duplications and translocations are typically
harmful
• Reciprocal translocation or inversion can alter
phenotype because a gene’s expression is
influenced by its location among neighboring
genes
Human disorders
• Several serious human disorders are due
to alterations of chromosome number and
structure
• Aneuploid zygotes
– Frequency is quite high
– Most are lethal (spontaneously aborted)
– Severe developmental problems result from
an imbalance among gene products
Aneuploid
• Certain aneuploid conditions upset the
balance less
– Making survival possible
– Surviving individuals have a set of symptoms
(syndrome)
• Characteristic of the type of aneuploidy
– Can be diagnosed by fetal testing before birth
Down Syndrome
• Trisomy 21
–
–
–
–
–
–
–
–
Characteristic facial features
Short stature
Heart defects
Susceptibility to respiratory infection
Mental retardation
Increased risk of developing leukemia
Increased risk of developing Alzheimer’s disease
Most are sexually underdeveloped and sterile
Down syndrome
• 1 in 700 children in the US
• Nondisjunction during gamete
production in one parent
• Frequency increases with
maternal age
– May be linked to age-dependent
abnormality in the spindle
checkpoint during meiosis I,
leading to nondisjunction
• Other trisomies also increase
with maternal age, but these
rarely for these infants to
survive long
Nondisjunction of sex
chromosomes
• Upsets genetic balance less severely than
autosomal aneuploidy
– Because the Y contains only a few genes
– Extra copies of X become Barr Bodies in
somatic cells
Disorders resulting from
Gamete nondisjunction
• XXY=Klinefelters
– 1 in 2000 births
– Have male sex organs
– But abnormally small testes and are sterile
– Extra X is inactivated, but some breast
enlargement and other female characteristics
are common
– Normal intelligence
Multiple Chromosome Defects:
Klinefelter’s Syndrome (46, XXY)
Trisomy X
• XXX
– 1 in 2000 live births
– Healthy females
– Both extra X are reduced to Barr body
Monosomy X
Turner Syndrome
• XO
– 1 in 5000 live births
– Only known viable monosomy in humans
– Phenotypically female
– Sterile, sex organs do not mature
– With estrogen therapy, secondary sex
characteristics form
– Most are of normal intelligence
Multiple Chromosome Defects:
Turner’s Syndrome (46, XO)
Alterations of chromosomes
• Can also cause
human disorders
• Deletions (even in
heterozygotes) can
cause severe
problems
• Cri du chat
– Specific deletion in
chromosome 5
– Mentally retarded,
small heads, unusual
facial features, cry
sounds like a mewing
of a distressed cat
– Fatal in infancy or
early childhood
Other translocations
• Between nonhomologous chromosomes
– Implicated in certain cancers
• Chronic myelogenous leukemia (CML)
• Large fragment of chromosome 22 switches places with
a small fragment from tip of chromosome 9
• The short, easily recognized chromosome 22 is called
the Philadelphia Chromosome
Normal chromosome 9
Reciprocal
translocation
Translocated chromosome 9
Philadelphia
chromosome
Normal chromosome 22
Figure 15.16
Translocated chromosome 22
Genomic imprinting
• Phenotypic effects of some mammalian
genes depend on whether they are
inherited from the mother or father
– Affects a few dozen identified genes (may be
many more)
– Not necessarily sex linked (may or may not lie
on the X chromosome)
– Occurs during formation of gametes
– Results in silencing of certain genes
• Imprinted genes are not expressed
Imprinting
• Some zygote genes are maternally imprinted
• Some are paternally imprinted
– Imprints are transmitted to all body cells during
development
– If maternally imprinted, then only parental allele is
expressed
– If paternally imprinted, then only maternal allele is
expressed
• Patterns of imprinting are characteristic for a
given species
Insulin-like growth factor
• Igf2
–
–
–
–
One of the first imprinted genes identified
Required for normal growth
Only the paternal allele is expressed
Evidence elucidated by crosses between wild type
mice and dwarf mice homozygous recessive for
mutation in Igf2
• Phenotypes of heterozygotes differ, depending on whether
the mutant allele comes from the mother or father
• Igf2 allele is imprinted in eggs, turning off expression of
imprinted allele
• In sperm Igf2 is not imprinted and functions normally
Genomic Imprinting: An
Example
What is genomic imprinting?
• Addition of methyl (-CH4) to cytosine
nucleotides on one of the alleles
• Hypothesis is that methylation silences an
allele
– Other mechanisms may lead to silencing of
imprinting genes
• Most of the known imprinted genes are
critical for embryonic development
In experiments..
• Mice embryos that inherit both copies of certain
chromosomes from the same parent die before
birth (regardless of whether parent is male or
female)
• Normal development requires embryonic cells
have one (and only one)active copy of certain
genes
• Abnormal imprinting is associated with abnormal
development and certain cancers
Extranuclear genes
• Small circles of DNA in
mitochondria and
chloroplasts
– Mitochondria and
chloroplasts reproduce
themselves and pass their
genes to daughter
organelles
• Do not display mendelian
inheritance
– Genes are not distributed
to offspring according to
the same rules of nuclear
chromosome distribution
First observed
• By Karl Correns in 1909
– Inheritance of patches of yellow or
white on the leaves of a green plant
– Determined the coloration of
offspring was determined by only
the maternal parent
– Coloration patterns are due to
genes in plastids inherited via the
ovum (NOT via the sperm)
Mitochondrial genes
• A zygote inherits all its mitochondria from
the ovum.
• All mitochondrial genes in mammals
demonstrate maternal inheritance
Human Disorders due to
mitochondrial DNA mutations
• Primarily impact ATP supply by producing defects
in Electron transport chain or ATP synthase
• Tissues requiring high energy needs may suffer
energy deprivation
• Mitochondrial myopathy
– Weakness, intolerance of exercise, muscle
deterioration
• Other mitochondrial mutations may contribute to
diabetes, heart disease and other diseases of
aging
Think about it:
Distinguish between sex-linked
disorders and sex chromosome
disorders.
Think about it:
•
•
Can you identify
the chromosome
abnormality in
this karyotype?
Is this individual a
male or a
female?
Think about it:
•
•
Can you identify
the chromosome
abnormality in this
karyotype?
Is this individual a
male or a female?
Think about it:
The ABO blood type locus has been
mapped on chromosome 9. A father
who has blood type AB and a
mother who has blood type O have
a child with trisomy 9 and blood type
A. Using this information, can you
tell in which parent the
nondisjunction occurred? Explain
your answer.