1. Chapter 24: Patterns of Chromosome Inheritance

2. 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.
All cells in the body except red blood cells have a nucleus and can the karyotyped. In adults, white blood cells are often selected for karyotyping. In fetuses, if abnormalities are suspected, cells can be obtained by either amniocentesis or chorionic villi sampling.

3. 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.

4. Amniocentesis
During amniocentesis, a long needle is use to withdraw amniotic fluid containing fetal cells. Biochemical tests can also be run on the amniotic fluid.

5. 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.

6. Chorionic villi sampling
During chorionic villi sampling, a suction tube is used to remove cells from the chorion, where the placenta will develop.

7. 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.

8. Human karyotype preparation
Cells are microscopically examined and photographed. A computer arranges the chromosomes into pairs based on size, shape, and banding patterns.

9. Normal male karyotype
Here is a karyotype of a normal male with 46 chromosomes.

10. Down syndrome karyotype
This karyotype shows an individual (male) with Down syndrome having an extra chromosome 21.

11. 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.
Trisomy is a condition in which there is an extra chromosome; monosomy is a condition in which there is one chromosome missing.

12. Nondisjunction in meiosis I
Nondisjunction can occur during meiosis I. The result is abnormal eggs with either one too many or one too few chromosomes. Fertilization with a normal sperm results in an abnormal number of chromosomes in the zygote. Note that two of the eggs could potentially have the correct number of chromosomes.

13. Nondisjunction in meiosis II
Nondisjunction can occur during meiosis II if the sister chromatids separate but the resulting chromosomes go into the same daughter cell. The egg has 24 chromosomes; after fertilization with normal sperm, the zygote would have 47 instead of the normal 46 chromosomes. Alternatively, the egg could have 22 chromosomes, so after fertilization, the zygote has 45 rather than 46 chromosomes.

14. 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.

15. Down Syndrome
Down 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.

16. Abnormal autosomal chromosome number
Persons with Down syndrome have an extra chromosome 21. Common characteristics include a wide, round face, and a fold on the upper eyelids. Mental retardation, along with an enlarged tongue, make it difficult for a person with Down syndrome to speak distinctly.

17. 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.

18. 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.

19. 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.
XO signifies the lack of a second X chromosome. Although their reproductive organs are underdeveloped, some females with Turner syndrome have given birth following in vitro fertilization using donor eggs.

20. 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.
Individuals with Klinefelter syndrome have large hands and feet and very long arms and legs.

21. Abnormal sex chromosome number
On the left is a female with Turner (XO) syndrome. She has a short, thick neck, short stature, and a lack of breast development. On the right is a male with Klinefelter (XXY) syndrome. He has immature sex organs and some development of the breasts.

22. Poly-X Females
A 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. Deletion
When chromosome 7 loses an end piece, the result is Williams syndrome. These children, although unrelated, have the same appearance, health, and behavioral problems. Children with this syndrome look like pixies because they have turned-up noses, wide mouths, a small chin, and large ears. Although their academic skills are poor, they exhibit excellent verbal and musical abilities.

28. 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.
Inverted means that the duplicated segment joins in the direction opposite from normal.

29. Duplication
When a piece of chromosome 15 is present in inverted sequence, a syndrome results in which the child has poor muscle tone and autistic characteristics.

30. 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.
A person who has both of the involved chromosomes has the normal amount of genetic material and is healthy, unless the chromosome exchange breaks an allele into two pieces.
The person who inherits only one of the translocated chromosomes will no doubt have only one copy of certain alleles and three copies of certain other alleles. A genetic counselor begins to suspect a translocation has occurred when spontaneous abortions are commonplace and family members suffer from various syndromes.

31. 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.

32. Translocation
When chromosomes 2 and 20 exchange segments, Alagille syndrome, with distinctive facial features, results. Here we see a father and son with Alagille syndrome. This father did not realize it until he had a child with the syndrome.

33. 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.

34. Inversion
A segment of one homologue is inverted. When crossing-over occurs during meiosis, both chromosomes end up having a duplication of some segments and a deletion of other segments.

35. Sex-Linked Traits
Traits 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.
Usually a sex-linked (X-linked) disorder is recessive; a female would have to inherit the disorder for both parents to express the disorder, while the male inherits it only from his mother who passes her X chromosome on to him.

36. X-Linked Alleles
The 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.
The inheritance from their father cannot offset the recessive allele because the Y chromosome does not carry X-linked alleles.

37. Cross involving an X-linked allele
The male parent is normal, but the female parent is a carrier; an allele for colorblindness is located on one of her X chromosomes. Therefore, each son stands a 50% chance of being color blind. The daughters will appear normal, but each one stands a 50% chance of being a carrier.

38. X-Linked Disorders
In 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.

39. X-linked recessive pedigree chart
Pedigree charts of X-linked recessive disorders show:
Males more than females are affected.
An affected son can have parents who have the normal phenotype.
For a female to have the characteristic, her father must also have it, and her mother either has it or is a carrier.
The characteristic often skips a generation from the grandfather to the grandson.
If a woman has the characteristic, all of her sons will have it.

40. 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.

41. Muscular Dystrophy
Muscular 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.

42. 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.

43. Hemophilia
Hemophilia 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.

44. Fragile X Syndrome
Fragile 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.

45. 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.

46. 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.

47. Linkage group
In this individual, alleles A and B are on one member of a homologous pair, and alleles a and b are on the other member. In complete linkage, the dihybrid produces only two types of gametes in equal proportion.

48. When linkage is incomplete, this dihybrid produces four types of gametes because crossing-over has occurred. The recombinant gametes occur in reduced proportion because crossing-over occurs infrequently.

49. 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.

50. Cross involving linked genes
Linked genes reduce the number of expected phenotypes among the offspring.

51. 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.

52. 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.