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Chapter 24: Patterns of Chromosome Inheritance

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Viewing the Chromosomes

A karyotype is a display of chromosomes paired according to their size, location of the centromere, and staining patterns.

A karyotype reveals abnormalities in chromosome number or structure.

Humans have 23 pairs of chromosomes; 22 pairs of autosomes and one pair of sex chromosomes.

Females are XX and males are XY.

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Amniocentesis

Amniocentesis uses a needle to extract amniotic fluid from the uterus of a pregnant woman from the 14th to 17th week of pregnancy.

Up to 400 chromosome and biochemical problems can be detected by culturing fetal cells that are in the amniotic fluid.

There is a slight risk of spontaneous abortion with this procedure.

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Amniocentesis

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Chorionic Villi Sampling

Chorionic villi sampling (CVS) uses a thin suction tube to sample chorionic cells from the placenta as early as the fifth week of pregnancy.

The cells do not have to be cultured, and karyotyping can be done immediately.

CVS carries a slightly greater risk of spontaneous abortion but can be performed earlier than amniocentesis.

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Chorionic villi sampling

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Karyotyping

Sampled fetal cells are stimulated to divide in culture medium and another chemical stops division during metaphase when chromosomes are highly condensed.

The stained cells are photographed and can be paired based on stained cross-bands, and size and shape.

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Human karyotype preparation

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Normal male karyotype

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Down syndrome karyotype

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Changes in Chromosome Number

Nondisjunction occurs during meiosis I when the members of a homologous pair both go into the same daughter cell or during meiosis II when the sister chromatids fail to separate and both daughter chromosomes go into the same gamete.

The result is a trisomy or a monosomy.

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Nondisjunction in meiosis I

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Nondisjunction in meiosis II

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Normal development depends on the presence of two of each kind of chromosome, but an extra chromosome is tolerated more than a missing chromosome.

The Barr body is an inactive X chromosome and is seen whenever more than one X chromosome is present (i.e., XX, XXY, XXX).

Cells of females function with a single chromosome just as those of males do.

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Down SyndromeDown syndrome is caused by trisomy 21,

three copies of chromosome 21 as a result of nondisjunction.

Symptoms include mental retardation, short stature, eyelid fold, flatter face, a palm creases, and stubby fingers, among others.

Nondisjunction usually occurred in producing the mother’s egg and risk increases at age 40.

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Abnormal autosomal chromosome number

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The genes causing Down syndrome are located on the bottom third of chromosome 21.

In particular, the Gart gene leads to a high level of purines, which contribute to mental impairment but may allow future preventive treatment.

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Changes in Sex Chromosome Number

The presence of a Y chromosome determines maleness.

The SRY gene on the short arm of the Y produces a testis-determining factor that begins the development of a male; otherwise an embryo develops as a female.

An abnormal number of sex chromosomes is the result of inheriting to many or too few X or Y chromosomes.

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Turner Syndrome

Individuals with Turner syndrome are females that have only one X chromosome; therefore they are XO.

They are short, with a broad chest, and webbed neck.

They do not undergo puberty or menstruate, and there is a lack of breast development.

Intelligence is normal and individuals can lead normal lives.

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Klinefelter Syndrome

Individuals with Klinefelter syndrome are males that have two or more X chromosomes in addition to a Y chromosome.

The Y chromosome drives development as a male but gonads are underdeveloped and breasts develop.

Klinefelter males are usually slow to learn but are not mentally retarded.

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Abnormal sex chromosome number

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Poly-X FemalesA poly-X female has more than two X

chromosomes and extra Barr bodies in the nucleus.

An XXX female has a normal phenotype except there may be menstrual difficulties, but she is fertile; her children usually have normal karyotypes.

Females with XXXX are usually tall and severely retarded; they may menstruate normally.

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Jacobs Syndrome

Jacobs syndrome males are XYY which can only result from nondisjuction during spermatogenesis.

They tend to be tall, have persistent acne, and have speech and reading problems.

At one time it was suggested that XYY males were unusually aggressive, but this was found not to be true.

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Changes in Chromosome Structure

A mutation is a permanent genetic change.

A change in chromosome structure is a chromosome mutation.

Radiation, organic chemicals, or even viruses may cause chromosomes to break, leading to mutations.

Chromosomal mutations include inversion, translocation, deletion, and duplication.

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Deletions and Duplications

Deletions occur when a single break causes a lost end piece, or two breaks result in a loss in the interior.

An individual who inherits a normal chromosome from one parent and a chromosome with a deletion from the other parent no longer has a pair of alleles for each trait, and a syndrome can result.

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In Williams syndrome, chromosome 7 loses an end piece and children have a pixie look and the skin ages prematurely from lack of the gene that governs elastin production.

An end piece of chromosome 5 produces cri du chat syndrome where larynx is abnormal and the infant’s cry is like that of a cat, the head is small, and there are facial abnormalities.

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Deletion

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Duplication results in a chromosome segment being repeated in the same chromosome or in a nonhomologous chromosome, producing extra alleles for a trait.

An inverted duplication in chromosome 15 causes inv dup 15 syndrome with poor muscle tone, mental retardation, and related symptoms.

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Duplication

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Translocation

Translocation is exchange of chromosomal segments between two, nonhomologous chromosomes.

In a small percent of cases, a translocation between chromosomes 21 and 14 causes Down syndrome.

The tendency for this particular translocation can run in the family of either the mother or father of affected individuals.

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Alagille syndrome results from a deletion of chromosome 20 or a translocation that disrupts an allele on chromosome 20.

The symptoms for Alagille syndrome range from mild to severe, so people may not be aware they have the syndrome.

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Translocation

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Inversion

Inversion involves a segment of a chromosome being turned 180 degrees; the reverse sequence of alleles can alter gene activity.

Crossing-over between inverted and normal chromosomes can cause recombinant chromosomes due to the inverted chromosome needing to form a loop to align.

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Inversion

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Sex-Linked TraitsTraits controlled by genes on the X or Y

chromosomes are sex-linked although most are unrelated to gender.

An allele on the X chromosome that is in the region where the Y chromosome has no alleles will express even if recessive; it is termed X-linked.

A female would have to have two recessive genes to express the trait; a male would only need one.

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X-Linked AllelesThe key for an X-linked problem shows

the allele attached to the X as in: XB = normal vision

Xb = color blindness. Females with the genotype XBXb are

carriers because they appear to be normal but each son has a 50% chance of being color blind depending on which allele the son receives.

XbXb and XbY are both colorblind.

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Cross involving an X-linked allele

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X-Linked DisordersIn pedigree charts that show the inheritance

pattern for X-linked recessive disorders, more males than females have the trait because recessive alleles on the X chromosome are expressed in males.

A grandfather passes an X-linked recessive disorder to a grandson through a carrier daughter.

X-linked recessive disorders include red-green color blindness, muscular dystrophy, and hemophilia.

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X-linked recessive pedigree chart

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Color Blindness

Three types of cones are in the retina detecting red, green, or blue.

Genes for blue cones are autosomal; those for red and green cones are on the X chromosome.

Males are much more likely to have red-green color blindness than females.

About 8% of Caucasian men have red-green color blindness.

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Muscular DystrophyMuscular dystrophy is characterized by

the wasting of muscles.

The most common form is Duchenne muscular dystrophy; this is an X-linked disorder, occurring in 1 of 3,600 males.

Muscles weaken, frequent falls and difficulty in rising occur early; death occurs by age 20.

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Duchenne muscular dystrophy involves the absence of a protein called dystrophin that is involved in the release of calcium from the sarcoplasmic reticulum of muscle cells.

The lack of dystrophin causes calcium to leak into the cell, which promotes the action of an enzyme that dissolves muscle fibers.

A test is now available to determine the carriers of Duchenne muscular dystrophy.

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HemophiliaHemophilia refers to the lack of one of

several clotting factors that leads to excessive bleeding in affected individuals.

Hemophiliacs bleed externally after injury, but also bleed internally around joints.

Hemorrhages can be stopped with blood transfusions or a biotechnology clotting factor.

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Fragile X SyndromeFragile X syndrome is an X-linked genetic

disorder with an unusual pattern of inheritance.

Individuals with this syndrome (one in 1,500 males and one in 2,500 females) have a base triplet repeat (CGG) in a gene on the X chromosome.

Children may be autistic or hyperactive with speech difficulties.

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Adults have large testes if male, and big protruding ears.

They are short in stature and the face is long with a prominent jaw.

A person with a smaller number of CGG repeats and minor or no symptoms is said to have a premutation and can pass it to their children where the number increases and the condition is severe.

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Linked Genes

All the alleles on one chromosome form a linkage group, which is inherited together.

If crossing-over occurs, a dihybrid cross gives all possible phenotypes among the offspring, but the expected ratio is greatly changed.

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Linkage group

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The frequency of recombinant gametes that occurs due to the process of crossing-over has been used to map chromosomes.

Crossing-over data is used to map the chromosomes of animals, such as fruit flies, but is limited in mapping human chromosomes because we do not control the crosses.

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Cross involving linked genes

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Chapter Summary

Humans normally inherit 22 pairs of autosomes and one pair of sex chromosomes for a total of 46 chromosomes.

Abnormalities arise when humans inherit an extra or missing autosome or abnormal autosomes.

In humans, males are normally XY and females are XX.

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Abnormalities arise when humans inherit an incorrect number of sex chromosomes.

Traits unrelated to the gender of an individual are controlled by genes located on the sex chromosomes.

Males express X-linked recessive disorders because they inherit only one X chromosome.

Genes that occur on the same chromosome form a linkage group and tend to be inherited together.