1. Chromosomes and Human Genetics
Chapter 12

2. Chromosomes & Cancer
Some genes on chromosomes control cell growth and division
If something affects chromosome structure at or near these loci, cell division may spiral out of control
This can lead to cancer

3. Philadelphia Chromosome
First abnormal chromosome to be associated with a cancer
Reciprocal translocation
Causes chronic myelogenous leukemia (CML)

4. Genes Units of information about heritable traits
In eukaryotes, distributed among chromosomes
Each has a particular locus
Location on a chromosome

5. Homologous Chromosomes
Homologous autosomes are identical in length, size, shape, and gene sequence
Sex chromosomes are nonidentical but still homologous
Homologous chromosomes interact, then segregate from one another during meiosis

6. Alleles Different molecular forms of a gene Arise through mutation
Diploid cell has a pair of alleles at each locus
Alleles on homologous chromosomes may be same or different

7. Sex Chromosomes Discovered in late 1800s Mammals, fruit flies
XX is female, XY is male
In other groups XX is male, XY female
Human X and Y chromosomes function as homologues during meiosis

8. Karyotype Preparation - Stopping the Cycle
Cultured cells are arrested at metaphase by adding colchicine
This is when cells are most condensed and easiest to identify

9. Karyotype Preparation
Arrested cells are broken open
Metaphase chromosomes are fixed and stained
Chromosomes are photographed through microscope
Photograph of chromosomes is cut up and arranged to form karyotype diagram

10. Karyotype Diagram Figure 12.4 Page 197 1 2 3 4 5 6 7 8 9 10 11 12
XX (or XY)
Figure 12.4 Page 197

11. Sex Determination female (XX) male (XY) eggs sperm Y X X x XX XY X Y
Figure 12.5 Page 198

12. The Y Chromosome Fewer than two dozen genes identified
One is the master gene for male sex determination
SRY gene (sex-determining region of Y)
SRY present, testes form
SRY absent, ovaries form

13. appearance of structures “uncommitted” duct system
that will give rise to
external genitalia
appearance of
“uncommitted” duct system
of embryo at 7 weeks
Effect of Y Chromosome
7 weeks Y
present Y
absent Y
present Y
absent
testes
ovaries
10 weeks
ovary
birth approaching
testis
Figure 12.6 Page 199

14. The X Chromosome Carries more than 2,300 genes
Most genes deal with nonsexual traits
Genes on X chromosome can be expressed in both males and females

15. Discovering Linkage homozygous dominant female recessive male Gametes:x X X X Y
All F1
have red eyes
Gametes: x X X X Y
1/2
1/2
1/4
1/2
1/2
1/4
1/4 F2
generation:
1/4
Figure 12.7 Page 200

16. Linkage Groups Genes on one type of chromosome Fruit flies
4 homologous chromosomes
4 linkage groups
Not all genes on chromosome are tightly linked

17. Full Linkage A B a b x Parents: A B a b AB ab F1 offspring: All AaBb
meiosis, gamete formation
Equal ratios of two types of gametes: A B a b
Figure 12.8a Page 201
50% AB
50% ab

18. Incomplete Linkage AC ac A C a c x Parents: A C a c F1 offspring:
All AaCc
meiosis, gamete formation A a A a
Unequal ratios of four types of gametes: C c c C
parental
genotypes
recombinant
genotypes
Figure 12.8b Page 201

19. Crossover Frequency Proportional to the distance that separates genesB C D
Crossing over will disrupt linkage between A and B more often than C and D
In-text figure Page 201

20. Linkage Mapping in Humans
Linkage maps based on pedigree analysis through generations
Color blindness and hemophilia are very closely linked on X chromosome

21. Pedigree Symbols male female marriage/mating
offspring in order of birth,
from left to right
Individual showing trait being studied
sex not specified
I, II, III, IV...
generation
Figure 12.9a Page 202

22. Pedigree for PolydactylyII
III IV V
female
male
5,5 6,6 *
5,5 6,6
6,6 5,5
6,6 5,5 6 7
5,5 6,6
5,5 6,6
5,5 6,6
5,5 6,6
5,6 6,7 12
6,6 6,6
*Gene not expressed in this carrier.
Figure 12.9b Page 202

23. Genetic Abnormality A rare, uncommon version of a trait Polydactyly
Unusual number of toes or fingers
Does not cause any health problems
View of trait as disfiguring is subjective

24. Genetic Disorder
Inherited conditions that cause mild to severe medical problems
Why don’t they disappear?
Mutation introduces new rare alleles
In heterozygotes, harmful allele is masked, so it can still be passed on to offspring

25. Autosomal Recessive Inheritance Patterns
If parents are both heterozygous, child will have a 25% chance of being affected
Figure 12.10a Page 204

26. Galactosemia Caused by autosomal recessive allele
Gene specifies a mutant enzyme in the pathway that breaks down lactose
lactose
galactose
enzyme 1
+ glucose
galactose-1-
phosphate
enzyme 2
galactose-1-
phosphate
enzyme 3
intermediate
in glycolysis
In-text figure Page 204

27. Autosomal Dominant Inheritance
Trait typically appears in every generation
Figure 12.10b Page 204

28. Huntington Disorder Autosomal dominant allele
Causes involuntary movements, nervous system deterioration, death
Symptoms don’t usually show up until person is past age 30
People often pass allele on before they know they have it

29. Achondroplasia Autosomal dominant allele
In homozygous form usually leads to stillbirth
Heterozygotes display a type of dwarfism
Have short arms and legs relative to other body parts

30. X-Linked Recessive Inheritance
Males show disorder more than females
Son cannot inherit disorder from his father
Figure 12.12a Page 205

31. Examples of X-Linked Traits
Color blindness
Inability to distinguish among some of all colors
Hemophilia
Blood-clotting disorder
1/7,000 males has allele for hemophilia A
Was common in European royal families

32. Fragile X Syndrome An X-linked recessive disorder
Causes mental retardation
Mutant allele for gene that specifies a protein required for brain development
Allele has repeated segments of DNA

33. Hutchinson-Gilford Progeria
Mutation causes accelerated aging
No evidence of it running in families
Appears to be dominant
Seems to arise as spontaneous mutation
Usually causes death in early teens

34. Duplication
Gene sequence that is repeated several to hundreds of times
Duplications occur in normal chromosomes
May have adaptive advantage
Useful mutations may occur in copy

35. Duplication
normal chromosome
one segment
repeated
three repeats

36. A linear stretch of DNA is reversed
Inversion
A linear stretch of DNA is reversed
within the chromosome
segments
G, H, I become inverted
In-text figure Page 206

37. Translocation
A piece of one chromosome becomes attached to another nonhomologous chromosome
Most are reciprocal
Philadelphia chromosome arose from a reciprocal translocation between chromosomes 9 and 22

38. Translocation one chromosome In-text figure Page 206 a nonhomologous
nonreciprocal translocation
In-text figure Page 206

39. Deletion Loss of some segment of a chromosome
Most are lethal or cause serious disorder

40. Aneuploidy Individuals have one extra or less chromosome
(2n + 1 or 2n - 1)
Major cause of human reproductive failure
Most human miscarriages are aneuploids

41. Polyploidy
Individuals have three or more of each type of chromosome (3n, 4n)
Common in flowering plants
Lethal for humans
99% die before birth
Newborns die soon after birth

42. nondisjunction at anaphase I
chromosome alignments at metaphase I
n - 1
nondisjunction at anaphase I
alignments at metaphase II
anaphase II
Figure Page 208

43. Down Syndrome Trisomy of chromosome 21
Mental impairment and a variety of additional defects
Can be detected before birth
Risk of Down syndrome increases dramatically in mothers over age 35

44. Turner Syndrome Inheritance of only one X (XO)
98% spontaneously aborted
Survivors are short, infertile females
No functional ovaries
Secondary sexual traits reduced
May be treated with hormones, surgery

45. Klinefelter Syndrome XXY condition
Results mainly from nondisjunction in mother (67%)
Phenotype is tall males
Sterile or nearly so
Feminized traits (sparse facial hair, somewhat enlarged breasts)
Treated with testosterone injections

46. XYY Condition Taller than average males
Most otherwise phenotypically normal
Some mentally impaired
Once thought to be predisposed to criminal behavior, but studies now discredit

47. Phenotypic Treatments
Symptoms of many genetic disorders can be minimized or suppressed by
Dietary controls
Adjustments to environmental conditions
Surgery or hormonal treatments

48. Genetic Screening
Large-scale screening programs detect affected persons
Newborns in United States routinely tested for PKU
Early detection allows dietary intervention and prevents brain impairment

49. Prenatal Diagnosis Amniocentesis Chorionic villus sampling Fetoscopy
All methods have some risks

50. Preimplantation Diagnosis
Used with in-vitro fertilization
Mitotic divisions produce ball of 8 cells
All cells have same genes
One of the cells is removed and its genes analyzed
If cell has no defects, the embryo is implanted in uterus