1. Chromosomes and Human Genetics
Chapter 15

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
Associated with a chronic leukemia
Overproduction of white blood cells

4. A Reciprocal Translocation1 2
Chromosome 9 and chromosome 22 exchanged pieces 6 13 15 19 20

5. An Altered Gene
When the reciprocal translocation occurred, a gene at the end of chromosome 9 fused with a gene from chromosome 22
This hybrid gene encodes an abnormal protein that stimulates uncontrolled division of white blood cells

6. Understanding Chromosomes
Walter Fleming
August Weismann
Rediscovery of Mendel’s work

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

8. 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

9. 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

10. 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

11. 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

12. 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

13. Human Karyotype
XX (or XY)

14. sex chromosome combinations possible in new individual
Sex Determination
eggs
sperm X Y X
Female germ cell
Male germ cell XX XY X Y
sex chromosome combinations possible in new individual

15. 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

16. 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

17. 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

18. Discovering Linkage One cross homozygous dominant female recessivex
Gametes: X Y
heterozygous
female
heterozygous
male
All F1 offspring have red eyes

19. Discovering Linkage Reciprocal cross homozygous recessive female
dominant
male x
Gametes: X X X Y
heterozygous
females
recessive
males
F1 offspring
Half are red-eyed females, half are white-eyed males

20. Discovering Linkage
Morgan’s crosses showed relationship between sex and eye color
Females can have white eyes
Morgan concluded gene must be on the X chromosome

21. Linkage Groups Genes on one type of chromosome Fruit flies Indian corn
4 homologous chromosomes
4 linkage groups
Indian corn
10 homologous chromosomes
10 linkage groups

22. Full Linkage Parents: F1 offspring:AB ab A B a b
Parents: x A B a b
F1 offspring:
All AaBb
meiosis, gamete formation A B a b
50%AB
50%ab
With no crossovers, half of the gametes have one parental genotype and half have the other

23. Incomplete Linkage Parents: F1 offspringAC ac A C a c
Parents: x A C a c
F1 offspring
All AaCc
meiosis, gamete formation
Unequal ratios of four types of gametes: A a A a C c c C
Most gametes have parental genotypes
A smaller number have recombinant genotypes

24. 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

25. Linkage Mapping in Humans
Linkage maps based on pedigree analysis through generations
Color blindness and hemophilia are very closely linked on X chromosome
Recombination frequency is 0.167%

26. Pedigree Chart that shows genetic connections among individuals
Standardized symbols
Knowledge of probability and Mendelian patterns used to suggest basis of a trait
Conclusions most accurate when drawn from large number of pedigrees

27. Pedigree for PolydactlyII
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.

28. 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

29. 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

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

31. Galactosemia Caused by autosomal recessive allele
Gene specifies a mutant enzyme in the pathway that breaks down lactose
enzyme 1
enzyme 2
enzyme 3
GALACTOSE-1-
PHOSOPHATE
GALACTOSE-1-
PHOSOPHATE
LACTOSE
GALACTOSE
+ glucose
intermediate
in glycolysis

32. Autosomal Dominant Inheritance
Trait typically appears in every generation

33. 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

34. Acondroplasia 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

35. X-Linked Recessive Inheritance
Males show disorder more than females
Son cannot inherit disorder from his father

36. 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

37. 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

38. Hutchinson-Guilford 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

39. 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

40. Duplication
normal chromosome
one segment repeated
three repeats

41. A linear stretch of DNA is reversed
Inversion
A linear stretch of DNA is reversed
within the chromosome

42. 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

43. Translocation chromosome nonhomologous chromosome
reciprocal translocation

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

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

46. 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

47. nondisjunction at anaphase I
chromosome alignments at metaphase I
n - 1
nondisjunction at anaphase I
alignments at metaphase II
anaphase II

48. 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

49. 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

50. 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

51. 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

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

53. 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

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

55. 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