1. Define the following terms and
utilize these terms in an appropriate context:
X-linked
Sex-linked
Sex-limited inheritance
Sex-influenced inheritance
allopolyploidy
aneuploidy
autopolyploidy
Barr body
chromosome abberation
chromosome mutation
deletion
Down syndrome
duplication
euploidy
inversion
monosomy
nondisjunction
paracentric inversion
translocation
trisomy
2. Compare the terms x-linked and sex-linked.
3. Compare the gene content of the X-chromosome and the Y-chromosome.
4. Outline all possible crosses between wild type (red eye) and white eyed Drosophila melanogaster to illustrate the inheritance of a sex-linked recessive trait.
5. Outline all possible crosses between bent and normal-tailed mice to illustrate the inheritance of a sex-linked dominant trait.
6. Explain why normal calico cats are females only, and describe the chromosome condition of male calico cats.
7. Describe the inheritance of the hairy ears characteristic in humans to illustrate a Y-linked trait.
8. Describe and explain sex-limited inheritance patterns and list some traits that display this pattern.
9. Differentiate between sex-influenced and sex-linked inheritance patterns.
10. Outline all possible crosses involving the gene for male pattern baldness to illustrate a sex-influenced trait.
11. Contrast the mechanisms underlying sex determination in humans compared to Drosophila.
12. Define a Barr body. Indicate the expected number of Barr bodies in the following individuals: Klinefelter syndrome; Turner syndrome; 47, XYY; 47, XXX; 47, XXXX.
13. Considering the information presented in an earlier unit about lethal genes, speculate as to why the vast majority of human 45,XX (orXY) conceptions fail to survive to birth.
14. Define and distinguidh between
the following pairs of terms:
aneuploidy/ euploidy
monosomy/ trisomy
autopolyploidy/ alloployploidy
paracentric inversion/ pericentric inversion.
15. Discuss evidence that suggests that Down syndrome is more often the result of nondisjunction during oogenesis rather than during spermatogenesis.
16. For a species with a diploid number of 18, indicate how many chromosomes will be present in the somatic nuclei of individuals who are haploid, triploid, tetraploid, trisomic, and monosomic.
17. Discuss the possible mechanisms involved in the production of deletions, duplications, inversions and translocations and also address the impact on the inheriter of these conditions.
18. Give some possible reasons why chromosome abberations are tolerated better by plants than by animals.
19. Give the general relationship between age and nondisjunction, and the specific relationshipbetween age of mother and frequency of non-disjunction of chromosome #21.
Resources: Text Chapter 4 pgs 79-83,
Text Chapter 8; Cartoon Guide pgs. 84-96
Sex Determination and Sex Linkage
Most organisms have chromosomal differences that determine sex, however, far from universal
Mammals, some insects, some plants --------------------->
XY System
Insects (grasshopper) ------------------------------------------->
XO System
Birds, most reptiles, butterflies ------------------------------->
ZW System
Heterogametic sex (produces two kinds of sex chromosomes)
Homogametic sex (produces one kind of sex chromosome)
In humans: male heterogametic, female homogametic
ZW system- opposite XY system because male is homogametic (ZZ) and females are heterogametic
Corn determined by the interaction of two
genes,
Inheritance of two dominants = normal hermaphrodite
Inheritance of one or the other dominant makes male or female
Inheritance of all recessives places female flowers where tassel should
be
In hymenopterans (bees, ants, wasps) unfertilized eggs become males, fertilized eggs become females. Males are haploid, females diploid.
In Drosophila sex determined by chromosome
ratios
questions that needed
to be answered:
1. in Drosophila is a male a male because he has a Y or because he has
only one X?
2. Is the female a female because she doesn't have the Y or because she
has two X's?
3. Do autosomes have anything to do with sex?
Calvin Bridges 1916- determined that critical factor in determining sex is the ratio
X chromosomes : haploid sets of autosomes
Normal ratio = 1.0 2A : 2X (fertile female)
3A : 3X (fertile female)
as ratio exceeds unity (3X : 2A = 1.5) ----> superfemale (meta female)
XXX; weak, infertile, low viability
XY normal male XXY normal female
XO sterile male YO lethal
led to indication that male determining factors may be found on autosomes
**female determining factors on X
Therefore, primary determination of male not because of the presence of
the Y but because of the lack of an X.
Conclusions:
1. sex generated by
ratio of X chromosome/ sets of autosomes
2. "maleness" carried
on autosomes
3. Y chromosome governs
fertility rather than sex XY and XO both males but only XY fertile
Sex determination in humans
1. autosomes play no
part in determining sex
2. The Y chromosome
determines maleness, even a single Y outweighing any number of X's
3. The X chromosome
determines femaleness in the absence of Y
1912 von Winiwarter determined humans have
47 chromosomes (male); females have 48.
geneticists of the time believed sex determined by presence of extra
1920 Theophilus Painter observed between 45- 48 chromosomes and discovered small Y chromo
1940- 1950 Accepted number of chromosomes 48
1956 Joe Han Tijo and Albert Levan ---> 46 diploid # (improvements in staining) one pair shown to vary in configuration; these designated sex chromosomes X and Y
**studies of Kleinfelters and Turners helped determine that Y contributes to maleness
Sexual Differentiation in humans (chromosomal
sex vs. Phenotypic sex)
-during early development,
every human embryo undergoes a period when it is potentially hermaphroditic
or bisexual
-external genitalia
indifferent (4-6 weeks establishment of gonadal sex)
if Y present ---> testes
if no Y ----------> ovary
*development of male dependent on gene products encoded by Y chromosome
*products stimulate differentiation, Near tip of short arm of Y chromosome lies TDF gene
Attempts made to document presence of genes
on Y chromosome:
such genes must show
Holandric or Y-linked inheritance patterns.
-Hairy pinna
-H-Y antigen (1955) common to all mammals studied at that time studies
proved XYY individual produces 2X more antigen than XY
Concluded that H-Y antigen was responsible for sex determination
-TDF (Testis Determining Factor); studies on "sex reversed" individuals
1987
Do XX males have a piece of Y?
Do XY females lack this piece? --------> YES
90 individuals in study showed perfect correlation
**Current belief is that the TDF region acts as a switch whose product
activates a group of other
genes influencing development
Sex-Linked Genes (X-linked inheritance)
Sex chromosomes- those chromosomes that play a role in sex Determination X and Y
Autosomes- all chromosomes that play no part in sex determination
Sex-linked (X-linked)- carried on X chromosome only; may be for traits associated with either sex
Inheritance of sex-linked recessive (book pgs 70-71)
Drosophila- white eye is recessive and located on the X-chromosome
w- white w+ (or+)= wild
Reciprocal Cross
P1 wild female X white male P1 white female X wild male
+ + X wY ww X +Y
Gametes + w; Y Gametes w +; Y
F1 +w and +Y F1 +w and wY
Gametes + or w + or Y Gametes + or w w or Y
F2
F2
Females all red: ++ or +w
1/4 red females +w, 1/4 white females ww
Males 50/50: red +Y, white wY
1/4 red males +Y, 1/4 white males wY
Human sex-linked recessives: colorblindness, hemophilia, muscular dystrophy (Duchenne Type) pg 71
Colorblindness pg 72
Characteristics of X-linked inheritance
1. most common in males
(only one X)
2. Criss-cross pattern
of inheritance (skips generations) expressed ---> carrier ---> expressed
---> carrier
3. Never have male
to male transmission (males give Y's to their sons)
4. affected males of
a kindred are always related through the females of that kindred
Sex-linked Dominant Bent tail in mice B- bent b- normal
Normal female bb X bent male BY
F1 Bb (bent females) or bY (normal males)
*affected males produce all affected females and no affected males
Bent female Bb X Bent male BY
F1 1/4 BB 1/4 Bb 1/4 BY 1/4 bY
*at least 1/2 of the offspring of affected females are affected regardless
of sex (try BbX by or
BB X bY)
Coat color in cats (calico) B- black Y- yellow (B and Y are codominant and sex linked)
Sex-Influenced Traits-genotypes determined by autosomal genes but expressed differently in sexes
Pattern Baldness in males (pg 73)- caused by autosomal allele that is dominant in males due to testosterone
B- bald b-normal
bb not bald
Bb not bald (females), bald (males)
BB bald females and females (females usually express to far less extent,
ex. thinning, and at later stages of life)
** more common in one sex than the other; autosomal; hormonal differences usually responsible
Sex-limited traits- expressed in
one sex only
1. milk production
2. Egg production
3. precocious puberty
(autosomal dominant) in males
Variations in Chromosome Structure and Arrangement
-deletions- portion
of chromosome lost
-duplications- addition
of chromosome parts
-inversions- portion
of chromosome detaches and makes 180 degree spin before reattaching
-translocations- portion
of chromosome detatches and becomes part of nonhomologous structure.
**variations most damaging in gametes rather than somatic cells.
A. Deletions (deficiency)
-may cause pseudodominance,
the expression of recessive traits due to absence of other allels (similar
to X chromosome in males)
1. Terminal Deletions
-due to one break
-end of chromosome lost
-generally lethal, but sometimes infants with small deficiencies survive
long enough to provide
observation (Cri-du-chat, deletion of short arm of chromosome #5)
2. Interstitial deletions
(intercalary)
-2 breaks
-section of chromosome deleted
-deletion loop
B. Duplications - addition
-usually lethal
-Down's imposter- partial trisomy of short arm of chromosome #12 attached
to chromosome #18
1. Originate by unequal crossing over
2. Types
a. Tandem
b. Reverse
c. Displaced
C. Inversions
-result from entanglement in meiosis
-fouls up normal chromosome pairing thus producing sterile individuals
1.
Inversion occurs between cuts
usually associated with loop formation
2. Two kinds of inversions
a. paracentric inversions- exclude centromere
b. paricentric inversions- include centromere
3. Crossing over with
a paracentric inversion, synapse requires a loop configuration
dicentric (2 centromeres)
acentric (no centromere)
-duplication/deficiency syndrome: cone shaped skull, distended veins on scalp, facial hair, glaucoma (hardening of eyeball), low set abnormal ears, short neck and limbs, cannot sit up, turnover or eat solid food.
-Duplication of long
arm #21, deficiency of short arm #21
D. Translocations
-part of chromosome
becomes detatched and joins part of a nonhomologous chromosome
-may occur between
nonhomologous parts of a homologous pair
a. Interstitial (Insertional or Transpositions; Transposons)
-part of a chromosome moved to another
b. reciprocal translocations- reciprocal exchange between 2 nonhomologous chromosomes
--reciprocal translocations responsible for 4-5% of all Down's cases
Familial Down's Syndrome
-results from nondisjunction at meiosis
-two nonhomologous arms come close enough to each other so that exchange
can occur
-genetic info lost or gained -inherited more frequently than trisomy
In Down's individual long arm of #21 attaches to #14. This individual has normal 46 chromosomes but because of the translocation, 3 copies of #21
Fragile sites in Humans
~1970 discovered some mitotic chromosomes with certain sections that would not stain giving appearance of gaps. Gaps appeared at different positions
-considered suceptible to chromosome breakage when cultured w/o folic acid
-correlation between one of the sites and a form of mental retardation
Fragile X Syndrome (fragile X-linked retardation; Martin-Bell Syndrome)
-folate senssitive site on X chromosome long narrow faces, protruding chins, large ears, increased testicular volume, varying degrees of mental retardation
females w/ one fragile and one normal show no clearcut physical characteristics
but show higher incidence of mental retardation
Variation in Chromosome Number and Arrangement
-quite different mechanism of phenotypic expression
-involve substantial modifications of chromosomes not genes
-taken together (change in # and arrangement) called "chromosome mutations", "chromosomal aberrations"
-follow Mendelian laws and are transmitted in predictable fashion
Variation in Chromosome Number
-range from addition
or loss of one or more chromosomes to addition of one or more haploid sets
Aneuploidy- gain or loss of one or more chromosomes but not complete set (most common: single chromosome is added to or lost from diploid set)
Results from nondisjunction- failure of sister chromatids in mitosis or homologous chromosomes in meiosis to separate and move to opposite poles of the division spindle
Monosomy- loss of one chromosome, produces a 2N - 1 compliment
Trisomy- gain of one chromosome, produces a 2N + 1 compliment
Tetrasomy- 2N + 2
Pentasomy- 2N + 3 etc.
Autosomal trisomies and monosomies usually lethal (due to aneuploid unbalanced
chromosome compliment)
Monosomy
-for one sex chromosome
is fairly common
-monosomy for autosomes
not easily tolerated, particularly in animals (why?)
-Because monosomy unmasks
recessive lethals that arre tolerated in heterozygotes
-expression of genetic
information during early development very delicately regulated
-Plant Kingdom more
tolerant but monosomies les viable
-autosomal monosomies
have not been reported beyond birth
Partial Monosomy: Cri-du-chat Syndrome
-loss of about 1/2 the short arm of chromosome 5 (46, 5p-)
-multiple anatomic malformations, gastrointestinal and cardiac complications,
severe retardation, glottis and larynx abnormal (cri-du-chat)
~1/50,000 live births
-size of deletion influences development (may learn verbal communication,
"trainable")
Trisomy- addition of extra chromosome
produces somewhat more variable individuals in plants and animals than
does loss
-in plants trisomics
are viable but phenotype may be altered EX. Jimson Weed
-in animals usually
severe defects, usually lethal during development (if autosomal)
Down's Syndrome- only human autosomal trisomy in which a significant # of individuals survive longer than a year past birth
Trisomy 21 47,21+ ~3/2000 infants (live births)
Most common case: nondisjunction during meiosis following fertilization
w/ normal gamete, trisomy
created, ovum (egg of female) most often the source
-short, epicanthic fold in corner of eye; small, round heads; protruding
tongue; short, broad hands; mental development retarded, IQ seldom above
70; shortened life expectancy
1/1000 freq at age 30; 1/100 at age 40; ~1/50 at age 45
Random occurrance, disorder not expected to be inherited, amniocentesis
Patau Syndrome- Trisomy 13 (47, 13+)
-not mentally alert, thought to be deaf, harelip, cleft palate, polydactyly,
congenital malformation of most
organs (indicative of abnormal development of 5 to 6 weeks of gestation)
survival ~6 months
-male and female parents average 32 years, not sure as to the origin of
nondisjunction 1/20,000 live
births
Edwards Syndrome- Trisomy 18 (47, 18+)
-smaller than average newborn, skulls elongated in anterior/posterior direction,
webbed neck, congenital
dislocation of hips, survival less than four months, average maternal age
34.7 years
-~1/8000 live births (about 80% of which are females)
Reduced Viability in Human Aneuploidy
15-20% of conceptions terminated spontaneously (some estimates are higher)
~30% of all spontaneous abortions demonstrate some chromosome anomalies
~90% of all chromosomal anomalies are terminated prior to birth, majority are aneuploids (trisomies; monosomies never found)
Support hypothesis that normal development
requires precise diploid compliment of chromosomes
Nondisjunction of Sex Chromosomes in
Humans
-somic condition tolerated to an extent in humans although phenotypically
abnormal
XXY- Klinefelters Syndrome (47, XXY) 2/1000 to
1/2000 live births
(48, XXXY; 48, XXYY; 49, XXXXY; 49, XXXYY) similar phenotypically, generally
more severe
manifestations are seen.
-sterile males w/some female characteristics, testes under develop, cannot
produce sperm
XO- Turners Syndrome (45, X) monosomic
-female external genetalia and ducts but ovaries underdeveloped, short,
webneck, broad chest.
1/5000 live births
Metafemale- XXX or XXXX ~1/1200 females; highly variable in expression
-underdeveloped secondary sex characteristics, sterile, retardation -presence
of extra X upsets
balances
XYY- males -above average height, can be subnormal in intelligence, personality disorders
-Witch hunt! 1968
Euploidy- three or more complete sets of chromosomes are found. (also called polyploidy). Multiples of n chromosome sets.
Diploidy 2N
Triploidy 3N
Tetraploidy; pentaploidy- 4N, 5N, etc.
*relitively infrequent in most animal species (exceptions are some lizards, amphibians, fish)
*much more common in plants (Nearly 1/2 including many important crops such as wheat, Hexaploid; potatoes, tetraploid; strawberries, octoploid)
*less frequent in animals because:
-sex determination more sensitive to polyploidy
-plants can self-fertilize, so single new polyploid can still produce.
-plants generally hybridize more easily with other related species
*odd numbers of chromosome sets not usually maintained reliably. Uneven numbers do not produce genetically balanced gametes.
Origins
Autopolyploids- receive all their chromosome sets from same species
Allopolyploids- receive chromosome sets from different species. Hybridization
Polyploidy: usually
leads to increase in cell size; often larger, more vigouous; triploids
usually sterile (seedless)
Cause: failure of all chromosomes to segregate during meiotic divisions Induced by: cold or heat shock during meiosis (applying colchicine during mitosis )
Allopolyploidy- hybrids -usually sterile
because inability to produce viable gametes due to inbalance of chromosomes
Examples 1.