Lecture Outline - Chapter 24

24.1. Inheritance of Chromosomes (p. 458)

1. Genes are on chromosomes.
2. Karyotype
   • a. Cells can be treated to enter a phase just prior to dividing.
   • b. Photographs of the chromosome spread can be cut apart or analyzed by computer.
   • c. Chromosomes occur in pairs and are arranged by size, shape, or banding pattern; resulting display of pairs of chromosomes is a karyotype. (Fig. 24.1)
   • d. Normally an individual receives 22 autosomal chromosomes and one sex chromosome from each parent, a total of 44 autosomes and two sex chromosomes.
   • e. Sex chromosomes include a larger X and a smaller Y; a male is XY and a female is XX.
3. Nondisjunction Causes Abnormalities (Fig. 24.2)
   • a. Abnormal numbers of autosomal chromosomes may be due to nondisjunction where chromosomes fail to separate after replication:
     • i. Can occur during meiosis I if homologous chromosomes fail to separate.
     • ii. Can occur during meiosis II if sister chromatids fail to separate.
   • b. Nondisjunction in an egg- or sperm-generating cell results in fertilized egg with:
     • i. Monosomy where karyotype is short by one chromosome (2n - 1).
     • ii. Trisomy where karyotype has an extra chromosome (2n + 1).
   • c. Many trisomies and most monosomies are fatal in humans.
   • d. Trisomy 18 (Edward syndrome) and trisomy 13 (Patau syndrome) have life span of less than one year.
   • e. Nondisjunction of sex chromosomes leads to XO, XXX, XXY, and XYY.
4. Down Syndrome (Fig. 24.3)
   • a. Most common autosomal trisomy is trisomy 21 also called Down syndrome.
   • b. Characteristics: short stature, rounded face, eyelid fold, fissured tongue, a palm crease, wide gap between first and second toes, and mental retardation (sometimes severe).
   • c. Extra 21st chromosome (three instead of two) usually due to egg nondisjunction; 24% of cases are from sperm carrying extra chromosome 21.
   • d. Chances of woman having a Down syndrome child increase with age; however most Down syndrome children are born to younger women due to much larger number of births.
   • e. Amniocentesis or chorionic villi testing riskier than having Down syndrome child; maternal blood test can now identify Down syndrome fetus.
   • f. Genes located on the bottom third of chromosome 21 may account for mental retardation; provides hope of future preventive treatment.
5. Chromosomal Mutations (p. 461)
   • a. Permanent changes in chromosome structure that can be detected microscopically are called chromosome mutations.
   • b. Radiation, organic chemicals, and viruses cause chromosomes to break apart.
   • c. If broken ends do not rejoin correctly, produces chromosome mutations. (Fig. 24.4)
     • i. Inversion occurs when chromosome segment is turned around 180 degrees; leads to altered gene activity.
     • ii. Translocation is movement of chromosomal segment to another nonhomologous chromosomes; in 5% of cases, translocation between chromosomes 21 and 14 is cause of Down syndrome.
     • iii. Deletion occurs when end of chromosome breaks off or when two simultaneous breaks result in loss of a segment; in cri du chat syndrome, portion of chromosome 5 is deleted; such individuals cry like a kitten and have mental retardation.
     • iv. Duplication results in a chromosomal segment occurring more than once in same chromosome; may be due to a broken segment attaching to its homologue or due to unequal crossing over; for instance, human cells have multiple copies of hemoglobin genes.

1. Sex chromosomes in humans are called X and Y.
   • a. Females are XX and egg can contain only an X.
   • b. Males are XY and sperm can contain X or Y.
   • c. All factors being equal, there is a 50% chance of having a boy or a girl.
   • d. More males are conceived but death rate among males is higher (more males spontaneously abort) until twice as many females as males at age 85.
2. Sex Chromosome Problems
   • a. Fragile X Syndrome
     • i. X chromosome is nearly broken; the tip hangs by a flimsy thread.
     • ii. More common by 25% in males over females.
     • iii. Children may be hyperactive, speech delayed, and repetitive.
     • iv. Adults have large testes, protruding ears and jaw, short stature.
     • v. Inherited in unusual pattern from male carrier to grandchild.
   • b. Abnormal Sex Chromosome Number (Fig. 24.5)
     • i. Turner Syndrome (Fig. 24.6)
       - XO indicates only one X chromosome, O is absencstit.
       - female due to absence of Y chromosome.
       - symptoms include a bull neck, short stature, nonfunctional ovaries, no puberty or menstruation or breast development.

       ii. Klinefelter Syndrome (Fig. 24.6b)

       - XXY or XXXY genotype.

       - male due to presence of Y.

       - testes and prostate are underdeveloped, some breast formation, no pubic or facial hair, and may have subnormal intelligence with more X chromosomes.

       iii. Metafemale

       - with three or more X chromosomes.

       - female due to absence of Y chromosome.

       - usually no apparent physical abnormalities except menstrual irregularities.

       iv. Jacobs Syndrome

       - XYY males.

       - these males are usually taller than average, have persistent acne, and tend to have speech and reading problems.
3. X Chromosomes and Barr Bodies
   • a. Females have condensed chromatin (inactive X chromosome) called Barr body.
   • b. Lyon hypothesis: female cells function with single X chromosome similar to males.
   • c. Therefore, normal males have no Barr body; XXY Klinefelter syndrome male has Barr body, XXX female has two, etc.
   • d. Either X chromosome in XX female's cells has 50% chance of being inactive Barr body; thus female's body is mosaic of cells with some expressing one X chromosome, others expressing the other X. (Fig. 24.7)
   • e. Lesch-Nyhan syndrome is recessive disorder of mental retardation, mutilating lips and fingers, formation of urinary stones, all due to lack of HGPRT enzyme; if woman is carrier, some of her hairs test positive, some negative.
   • f. Female carrier for Duchenne muscular dystrophy shows mosaic muscle cell test.

1. Series of genes on Y chromosome determine testes development; gene on X determines ovary development.
2. Other traits on sex chromosome are termed sex linked traits.
3. Alleles found on larger X chromosome are called X-linked.
4. The few alleles found on Y chromosome are called Y-linked.
5. Male always receives X-linked condition from his mother (where he received X chromosome).
6. Female must receive two alleles, one from each parent, to express recessive traits.
7. Solving X-Linked Genetics Problems (p. 467)
   • a. Superscripts indicate the traits on sex chromosomes, except for Y chromosome region that lacks genes.
   • b. Color Blindness
     • i. Recessive gene found on X chromosome.
     • ii. X^B is normal vision and X^b is color blindness.
     • iii. X^BX^B is homozygous female with normal color vision.
     • iv. X^BX^b is carrier female with normal color vision.
     • v. X^bX^b = color-blind female.
     • vi. X^BY = normal vision male.
     • vii. X^bY = color-blind male.
   • c. Inheritance pattern is seen in Punnett square Figure 24.8.
8. X-linked Recessive Disorders (Fig. 24.9) (p. 468)
   • a. Color Blindness
     • i. Three genes involved in distinguishing color because three different types of cones.
     • ii. Two forms of color blindness involves gene affecting green-sensitive cones or gene affecting red-sensitive cones.
     • iii. Recessive mutation affects 5% of Caucasian men for green color perception, 2% for red perception.
   • b. Hemophilia
     • i. Termed bleeder's disease because clotting factor VIII is missing.
     • ii. Danger from internal bleeding; hemorrhages can be sealed with transfusion of blood or clotting protein.
     • iii. European royal families trace hemophilia of males to Queen Victoria. (Fig. 24.10)
   • c. Muscular Dystrophy
     • i. Muscles waste away.
     • ii. Duchenne muscular dystrophy is most common form, one in 3,600 males.
     • iii. Symptoms include frequent falls, difficulty rising, confinement to wheelchair, and death by age 20.
     • iv. Absence of protein dystrophin causes a leakage of calcium from storage sacs within the cell into the rest of the cell; promotes enzyme that dissolves muscle fiber.
     • v. Body's attempt to repair tissue results in fibrous tissue that cuts off blood supply.
     • vi. Gene has recently been isolated; tests for carriers are available; treatments are being tested.
9. Sex-Influenced Traits (p. 470)
   • a. Not all traits associated with gender are sex-linked.
   • b. Some are simply sex-influenced but located on autosomal genes.
   • c. Sex hormones might determine if genes are expressed.
   • d. Or hormone effects may require one allele to be expressed in males, two in females, acting as if dominant in males, recessive in females.
   • e. Pattern baldness occurs with added testosterone; requires only one gene for trait to appear; in females requires two genes. (Fig. 24.11)
   • f. Finger length in males: index finger is shorter than fourth finger, shorter in females.

1. Chromosome map gives order of various gene loci on a particular chromosome.
2. Linkage Data. (Fig. 24.12)
3. All genes on a chromosome form a linkage group because they are inherited together.
4. By studying crossover frequency of linked genes, a chromosomal map can be made.
   • a. Distant genes are more likely to be separated by crossing over than genes that are close together.
   • b. Each 1% of recombination frequency is equivalent to one map unit.
   • c. ABO blood group and nail-patella syndrome (NPS) are on same chromosome.
     • i. In family with these chromosomes, 10% of children had recombinant phenotypes, 5% had type B but no NPS and 5% had type O and NPS.
     • ii. Suggests that two genes are ten map units apart.
5. Linkage data easily map chromosomes of fruit fly where crosses are controlled; human data is limited by uncontrolled (by science) matings, and few young produced.
6. Human Genome Project
   • a. Goal is to identify the location of approximately 100,000 human genes, called a genetic map.
   • b. Also attempts to determine sequence of three billion bases in human genome, called the physical map.
   • c. The Genetic Map
     • i. mRNA is isolated; reverse transcriptase produces a cDNA copy of gene; cDNA attached to fluorescent dye is probe to locate chromosome and band location right on microscope slide.
     • ii. Genetic marker is place on chromosome where base sequence differs from person to person (often in "filler DNA" sequences between genes); use of restriction enzymes cleaves DNA into fragments; RFLPs (restriction fragment length polymorphisms) can be used to assign gene location on chromosome and test for genetic disorders.
     • iii. Tests available for sickle-cell disease, Huntington disease, Duchenne muscular dystrophy. (Fig. 24.13)
   • d. The Physical Map
     • i. Lab procedures can determine sequence of DNA pairs. (Fig. 24.14)
     • ii. Genetic markers contain unique stretches of DNA called expressed sequence tags (ESTs); these link genetic map with physical map.