1. Chromosomes and Human Inheritance
Chapter 12

2. Impacts, Issues: Strange Genes, Tortured Minds
Exceptional creativity often accompanies neurobiological disorders such as schizophrenia, autism, chronic depression, and bipolar disorder
Examples: Lincoln, Woolf, and Picasso

3. 12.1 Human Chromosomes
In humans, two sex chromosomes are the basis of sex – human males have XY sex chromosomes, females have XX
All other human chromosomes are autosomes – chromosomes that are the same in males and females

4. Sex Determination in Humans
Sex of a child is determined by the father
Eggs have an X chromosome; sperm have X or Y

5. Sex Determination in Humans
The SRY gene on the Y chromosome is the master gene for male sex determination
Triggers formation of testes, which produce the male sex hormone (testosterone)
Without testosterone, ovaries develop and produce female sex hormones (estrogens)

6. Sexual Development in Humans

7. diploid germ cells in female diploid germ cells in male
meiosis, gamete formation in both female and male:
eggs
sperm X × Y X × X
fertilization: X X
Figure 12.2
(a) Punnett-square diagram showing the sex determination pattern in humans. (b) An early human embryo appears neither male nor female. Then tiny ducts and other structures that can develop into male or female reproductive organs start forming. In an XX embryo, ovaries form in the absence of the Y chromosome and its SRY gene. In an XY embryo, the gene product triggers formation of testes, which secrete a hormone that initiates development of other male traits. (c) External reproductive organs in human embryos. X XX XX Y XY XY
sex chromosome combinations possible in the new individual
Fig. 12-2a, p. 186

8. Figure 12.2
(a) Punnett-square diagram showing the sex determination pattern in humans. (b) An early human embryo appears neither male nor female. Then tiny ducts and other structures that can develop into male or female reproductive organs start forming. In an XX embryo, ovaries form in the absence of the Y chromosome and its SRY gene. In an XY embryo, the gene product triggers formation of testes, which secrete a hormone that initiates development of other male traits. (c) External reproductive organs in human embryos.
Fig. 12-2bc, p. 186

9. At seven weeks, appearance of “uncommitted” duct system of embryo
At seven weeks, appearance of structures that will give rise to external genitalia
Y chromosome present
Y chromosome absent
Y chromosome present
Y chromosome absent
testes
ovaries
10 weeks
10 weeks
Figure 12.2
(a) Punnett-square diagram showing the sex determination pattern in humans. (b) An early human embryo appears neither male nor female. Then tiny ducts and other structures that can develop into male or female reproductive organs start forming. In an XX embryo, ovaries form in the absence of the Y chromosome and its SRY gene. In an XY embryo, the gene product triggers formation of testes, which secrete a hormone that initiates development of other male traits. (c) External reproductive organs in human embryos.
ovary
penis
vaginal opening
uterus
penis
vagina
testis
birth approaching b c
Fig. 12-2bc, p. 186

10. Animation: Human sex determination

11. Karyotyping Karyotype Construction of a karyotype
A micrograph of all metaphase chromosomes in a cell, arranged in pairs by size, shape, and length
Detects abnormal chromosome numbers and some structural abnormalities
Construction of a karyotype
Colchicine stops dividing cells at metaphase
Chromosomes are separated, stained, photographed, and digitally rearranged

12. Karyotyping

13. Figure 12.3
Karyotyping, a diagnostic tool that reveals an image of a single cell’s diploid complement of chromosomes. This human karyotype shows 22 pairs of autosomes and a pair of X chromosomes.
Figure It Out: Was this cell taken from a male or female?
Answer: Female
Fig. 12-3a, p. 187

14. Figure 12.3
Karyotyping, a diagnostic tool that reveals an image of a single cell’s diploid complement of chromosomes. This human karyotype shows 22 pairs of autosomes and a pair of X chromosomes.
Figure It Out: Was this cell taken from a male or female?
Answer: Female
Fig. 12-3b, p. 187

15. Animation: Karyotype preparation

16. 12.1 Key Concepts Autosomes and Sex Chromosomes
All animals have pairs of autosomes – chromosomes that are identical in length, shape, and which genes they carry
Sexually reproducing species also have a pair of sex chromosomes; the members of this pair differ between males and females

17. 12.2 Autosomal Inheritance Patterns
Many human traits can be traced to autosomal dominant or recessive alleles that are inherited in Mendelian patterns
Some of those alleles cause genetic disorders

18. Autosomal Dominant Inheritance
A dominant autosomal allele is expressed in homozygotes and heterozygotes
Tends to appear in every generation
With one homozygous recessive and one heterozygous parent, children have a 50% chance of inheriting and displaying the trait
Examples: achondroplasia, Huntington’s disease

19. Autosomal Recessive Inheritance
Autosomal recessive alleles are expressed only in homozygotes; heterozygotes are carriers and do not have the trait
A child of two carriers has a 25% chance of expressing the trait
Example: galactosemia

20. Autosomal Inheritance

21. Figure 12.4
(a) Example of autosomal dominant inheritance. A dominant allele (red) is fully expressed in heterozygotes. Achondroplasia, an autosomal dominant disorder, affects the three men shown above. At center, Verne Troyer (Mini Me in the Mike Myers spy movies), stands two feet, eight inches tall. (b) An autosomal recessive pattern. In this example, both parents are heterozygous carriers of the recessive allele (red).
Fig. 12-4a, p. 188

22. Figure 12.4
(a) Example of autosomal dominant inheritance. A dominant allele (red) is fully expressed in heterozygotes. Achondroplasia, an autosomal dominant disorder, affects the three men shown above. At center, Verne Troyer (Mini Me in the Mike Myers spy movies), stands two feet, eight inches tall. (b) An autosomal recessive pattern. In this example, both parents are heterozygous carriers of the recessive allele (red).
Fig. 12-4b, p. 188

23. Animation: Autosomal dominant inheritance

24. Animation: Autosomal recessive inheritance

25. Galactosemia

26. Neurobiological Disorders
Most neurobiological disorders do not follow simple patterns of Mendelian inheritance
Depression, schizophrenia, bipolar disorders
Multiple genes and environmental factors contribute to NBDs

27. 12.3 Too Young to be Old Progeria
Genetic disorder that results in accelerated aging
Caused by spontaneous mutations in autosomes

28. 12.2-12.3 Key Concepts Autosomal Inheritance
Many genes on autosomes are expressed in Mendelian patterns of simple dominance
Some dominant or recessive alleles result in genetic disorders

29. 12.4 Examples of X-Linked Inheritance
X chromosome alleles give rise to phenotypes that reflect Mendelian patterns of inheritance
Mutated alleles on the X chromosome cause or contribute to over 300 genetic disorders

30. X-Linked Inheritance Patterns
More males than females have X-linked recessive genetic disorders
Males have only one X chromosome and can express a single recessive allele
A female heterozygote has two X chromosomes and may not show symptoms
Males transmit an X only to their daughters, not to their sons

31. X-Linked Recessive Inheritance Patterns

32. Animation: X-linked inheritance

33. Some X-Linked Recessive Disorders
Hemophilia A
Bleeding caused by lack of blood-clotting protein
Red-green color blindness
Inability to distinguish certain colors caused by altered photoreceptors in the eyes
Duchenne muscular dystrophy
Degeneration of muscles caused by lack of the structural protein dystrophin

34. Hemophilia A in Descendents of Queen Victoria of England

35. Red-Green Color Blindness

36. Figure 12.9
Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8.
Fig. 12-9a, p. 191

37. Figure 12.9
Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8.
Fig. 12-9b, p. 191

38. Figure 12.9
Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8.
Fig. 12-9c, p. 191

39. Figure 12.9
Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8.
Fig. 12-9d, p. 191

40. 12.4 Key Concepts Sex-Linked Inheritance
Some traits are affected by genes on the X chromosome
Inheritance patterns of such traits differ in males and females

41. 12.5 Heritable Changes in Chromosome Structure
On rare occasions, a chromosome’s structure changes; such changes are usually harmful or lethal, rarely neutral or beneficial
A segment of a chromosome may be duplicated, deleted, inverted, or translocated

42. Duplication
DNA sequences are repeated two or more times; may be caused by unequal crossovers in prophase I

43. normal chromosome
one segment repeated
p. 192

44. Deletion
Loss of some portion of a chromosome; usually causes serious or lethal disorders
Example: Cri-du-chat

45. segment C deleted
p. 192

46. Deletion: Cri-du-chat

47. Figure 12.10
Cri-du-chat syndrome. (a) This infant’s ears are low relative to his eyes. (b) Same boy, four years later. The high-pitched monotone of cri-du-chat children may persist into their adulthood.
Fig a, p. 192

48. Figure 12.10
Cri-du-chat syndrome. (a) This infant’s ears are low relative to his eyes. (b) Same boy, four years later. The high-pitched monotone of cri-du-chat children may persist into their adulthood.
Fig b, p. 192

49. Inversion
Part of the sequence of DNA becomes oriented in the reverse direction, with no molecular loss

50. segments G, H, I become inverted
p. 192

51. Translocation
Typically, two broken chromosomes exchange parts (reciprocal translocation)

52. nonhomologous chromosome
reciprocal translocation
p. 192

53. Does Chromosome Structure Evolve?
Changes in chromosome structure can reduce fertility in heterozygotes; but accumulation of multiple changes in homozygotes may result in new species
Certain duplications may allow one copy of a gene to mutate while the other carries out its original function

54. Differences Among Closely Related Organisms
Humans have 23 pairs of chromosomes; chimpanzees, gorillas, and orangutans have 24
Two chromosomes fused end-to-end

55. human chimpanzee gorilla orangutan Figure 12.11
Banding patterns of human chromosome 2 (a), compared with two chimpanzee chromosomes (b). Bands appear because different regions of the chromosomes take up stain differently.
human
chimpanzee
gorilla
orangutan
Fig , p. 193

56. Evolution of X and Y Chromosomes from Homologous Autosomes

57. areas that cannot cross over SRY
Ancestral reptiles
Ancestral reptiles Y X
Monotremes Y X
Marsupials Y X
Monkeys Y X
Humans Y X
(autosome pair)
areas
that can cross over
areas that cannot cross over
SRY
A Before 350
mya, sex was determined by temperature, not by chromosome differences.
B SRY gene
evolves 350 mya. Other mutations accumulate and
the chromosomes of the pair diverge.
C By 320–240 mya, the two chromosomes have diverged so much that they no longer cross
over in one region. The
Y chromosome begins
to degenerate.
D Three more times, 170–130 mya, the pair stops crossing over in another region. Each time, more changes accumulate, and the Y chromosome gets shorter. Today, t
he pair crosses over only at a small region near the ends.
Figure 12.12
Evolution of the Y chromosome. Mya stands for million years ago.
Fig , p. 193

58. 12.6 Heritable Changes in the Chromosome Number
Occasionally, new individuals end up with the wrong chromosome number
Consequences range from minor to lethal
Aneuploidy
Too many or too few copies of one chromosome
Polyploidy
Three or more copies of each chromosome

59. Nondisjunction
Changes in chromosome number can be caused by nondisjunction, when a pair of chromosomes fails to separate properly during mitosis or meiosis
Affects the chromosome number at fertilization
Monosomy (n-1 gamete)
Trisomy (n+1 gamete)

60. Nondisjunction

61. Autosomal Change and Down Syndrome
Only trisomy 21 (Down syndrome) allows survival to adulthood
Characteristics include physical appearance, mental impairment, and heart defects
Incidence of nondisjunction increases with maternal age
Can be detected through prenatal diagnosis

62. Trisomy 21

63. chromosome alignments at metaphase I CHROMOSOME NUMBER IN GAMETES
Figure 12.13
(a) A case of nondisjunction. This karyotype reveals the trisomic 21 condition of a human female. (b) One example of how nondisjunction arises. Of the two pairs of homologous chromosomes shown here, one fails to separate during anaphase I of meiosis. The chromosome number is altered in the gametes that form after meiosis.
n − 1
chromosome alignments at metaphase I
CHROMOSOME NUMBER
IN GAMETES
NONDISJUNCTION AT ANAPHASE I
alignments at metaphase II
anaphase II
Fig b, p. 194

64. chromosome alignments at metaphase I NONDISJUNCTION AT ANAPHASE I
alignments at metaphase II
anaphase II
n + 1
n − 1
CHROMOSOME NUMBER
IN GAMETES
Figure 12.13
(a) A case of nondisjunction. This karyotype reveals the trisomic 21 condition of a human female. (b) One example of how nondisjunction arises. Of the two pairs of homologous chromosomes shown here, one fails to separate during anaphase I of meiosis. The chromosome number is altered in the gametes that form after meiosis.
Stepped Art
Fig b, p. 194

65. Down Syndrome and Maternal Age

66. Figure 12.14
Relationship between the frequency of Down syndrome and mother’s age at childbirth. The data are from a study of 1,119 affected children. The risk of having a trisomic 21 baby rises with the mother’s age. About 80 percent of trisomic 21 individuals are born to women under thirty-five, but these women have the highest fertility rates, and they have more babies.
Fig a, p. 195

67. Figure 12.14
Relationship between the frequency of Down syndrome and mother’s age at childbirth. The data are from a study of 1,119 affected children. The risk of having a trisomic 21 baby rises with the mother’s age. About 80 percent of trisomic 21 individuals are born to women under thirty-five, but these women have the highest fertility rates, and they have more babies.
Fig b, p. 195

68. Change in Sex Chromosome Number
Changes in sex chromosome number may impair learning or motor skills, or be undetected
Female sex chromosome abnormalities
Turner syndrome (XO)
XXX syndrome (three or more X chromosomes)
Male sex chromosome abnormalities
Klinefelter syndrome (XXY)
XYY syndrome

69. Turner Syndrome XO (one unpaired X chromosome)
Usually caused by nondisjunction in the father
Results in females with undeveloped ovaries

70. 12.5-12.6 Key Concepts: Changes in Chromosome Structure or Number
On rare occasions, a chromosome may undergo a large-scale, permanent change in its structure, or the number of autosomes or sex chromosomes may change
In humans, such changes usually result in a genetic disorder

71. 12.7 Human Genetic Analysis
Charting genetic connections with pedigrees reveals inheritance patterns for certain alleles
Pedigree
A standardized chart of genetic connections
Used to determine the probability that future offspring will be affected by a genetic abnormality or disorder

72. Studying Inheritance in Humans
Genetic studies can reveal inheritance patterns or clues to past events
Example: A link between a Y chromosome and Genghis Khan?

73. Defining Genetic Disorders and Abnormalities
Genetic abnormality
A rare or uncommon version of a trait; not inherently life threatening
Genetic disorder
An inherited condition that causes mild to severe medical problems, characterized by a specific set of symptoms (a syndrome)

74. Some Human Genetic Disorders and Genetic Abnormalities

75. Stepped Art
Table 12-1, p. 196

76. Recurring Genetic Disorders
Mutations that cause genetic disorders are rare and put their bearers at risk
Such mutations survive in populations for several reasons
Reintroduction by new mutations
Recessive alleles are masked in heterozygotes
Heterozygotes may have an advantage in a specific environment

77. A Pedigree for Huntington’s Disease
A progressive degeneration of the nervous system caused by an autosomal dominant allele

78. Constructing a Pedigree for Polydactyly

79. Animation: Pedigree diagrams

80. 12.8 Prospects in Human Genetics
Genetic analysis can provide parents with information about their future children
Genetic counseling
Starts with parental genotypes, pedigrees, and genetic testing for known disorders
Information is used to predict the probability of having a child with a genetic disorder

81. Prenatal Diagnosis
Tests done on an embryo or fetus before birth to screen for sex or genetic problems
Involves risks to mother and fetus
Three types of prenatal diagnosis
Amniocentesis
Chorionic villus sampling (CVS)
Fetoscopy

82. Amniocentesis

83. Animation: Amniocentesis

84. Fetoscopy

85. Preimplantation Diagnosis
Used in in-vitro fertilization
An undifferentiated cell is removed from the early embryo and examined before implantation

86. After Preimplantation Diagnosis
When a severe problem is diagnosed, some parents choose an induced abortion
In some cases, surgery, prescription drugs, hormone replacement therapy, or dietary controls can minimize or eliminate symptoms of a genetic disorder
Example: PKU can be managed with dietary restrictions

87. Genetic Screening
Genetic screening (widespread, routine testing for alleles associated with genetic disorders)
Provides information on reproductive risks
Identifies family members with a genetic disorder
Used to screen newborns for certain disorders
Used to estimate the prevalence of harmful alleles in a population

88. 12.7-12.8 Key Concepts Human Genetic Analysis
Various analytical and diagnostic procedures often reveal genetic disorders
What an individual, and society at large, should do with the information raises ethical questions

89. Animation: Deletion

90. Animation: Duplication

91. Animation: Inversion

92. Animation: Morgan’s reciprocal crosses

93. Animation: Translocation

94. Video: Strange genes, richly tortured minds