1. Sex Determination in Humans
Chromosomal sex is determined at fertilization
Sexual differences begin in the 7th week
Sex is influenced by genetic and environmental factors
Females (generally XX) do not have a Y chromosome
Males (generally XY) have a Y chromosome
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

2. Fig. 7.10
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

3. Defining Sex Chromosomal sex Gonadal sex Phenotypic sex
Formation of male or female reproductive structures depends on
Gene action
Interactions within the embryo
Interactions with other embryos in the uterus
Interactions with the maternal environment
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

4. Sex Differentiation
In early embryo there are two internal duct systems
Wolffian (male)
Müllerian (female)
At 7 weeks, developmental pathways activate different sets of genes
Cause undifferentiated gonads to develop as testes or ovaries
Determine the gonadal sex of embryo
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

5. Appearance of “uncommitted” duct system of embryo at 7 weeks
Y chromosome present
Y chromosome absent
FIGURE 7.12 (b) Two duct systems (Wolffian and Müllerian) are present in the early embryo. They enter different developmental pathways in the presence and absence of a Y chromosome.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-12b, p.167

6. Appearance of “uncommitted” duct system of embryo at 7 weeks
Y chromosome present
Y chromosome absent
Testes
Ovaries
FIGURE 7.12 (b) Two duct systems (Wolffian and Müllerian) are present in the early embryo. They enter different developmental pathways in the presence and absence of a Y chromosome.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-12b, p.167

7. Appearance of “uncommitted” duct system of embryo at 7 weeks
Y chromosome present
Y chromosome absent
Testes
Ovaries
FIGURE 7.12 (b) Two duct systems (Wolffian and Müllerian) are present in the early embryo. They enter different developmental pathways in the presence and absence of a Y chromosome.
Uterus
Ovary
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Penis
Vagina
Stepped Art
Testis
Fig. 7-12b, p.167

8. Appearance of structures that will give rise to external genitalia
7 weeks
Y chromosome present
Y chromosome absent
FIGURE 7.12 (c) Steps in the development of phenotypic sex from an undifferentiated stage to the male or female phenotype. The male pathway of development takes place in response to the presence of a Y chromosome and production of the hormones testosterone and dihydrotestosterone (DHT). Female development takes place in the absence of a Y chromosome and without these hormones.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-12c, p.167

9. Appearance of structures that will give rise to external genitalia
7 weeks
Y chromosome present
Y chromosome absent
10 weeks
10 weeks
FIGURE 7.12 (c) Steps in the development of phenotypic sex from an undifferentiated stage to the male or female phenotype. The male pathway of development takes place in response to the presence of a Y chromosome and production of the hormones testosterone and dihydrotestosterone (DHT). Female development takes place in the absence of a Y chromosome and without these hormones.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-12c, p.167

10. Appearance of structures that will give rise to external genitalia
7 weeks
Y chromosome present
Y chromosome absent
10 weeks
10 weeks
FIGURE 7.12 (c) Steps in the development of phenotypic sex from an undifferentiated stage to the male or female phenotype. The male pathway of development takes place in response to the presence of a Y chromosome and production of the hormones testosterone and dihydrotestosterone (DHT). Female development takes place in the absence of a Y chromosome and without these hormones.
Penis
Vaginal
opening
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Birth approaching
Birth approaching
Fig. 7-12c, p.167

11. Genes on the Y Chromosome
Cause the indifferent gonad to develop as a testis
Sex determining region is the SRY gene
Other genes on the autosomes play an important role
Once testes develop they secrete two hormones
Testosterone
Müllerian Inhibiting Hormone (MIH)
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

12. Females Develop in the Absence of Y
Embryonic gonads develop into an ovaries
Testosterone not produced
Wolffian system degenerates
MIH is not produced
Müllerian duct system develops to form oviduct, uterus and parts of the vagina
Sexual phenotype develops
Hormones are important
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

13. Stepped Art Fig. 7-13, p.168 Male Egg with X sex chromosome Female
FIGURE 7.13 The major pathways of sexual differentiation and the stages at which genetic sex, gonadal sex, and phenotypic sex are established.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-13, p.168

14. Sperm with Y chromosome
Male
Egg with X sex chromosome
Female
Fertilized by
Fertilized by
Sperm with Y chromosome
Sperm with X chromosome
FIGURE 7.13 The major pathways of sexual differentiation and the stages at which genetic sex, gonadal sex, and phenotypic sex are established.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-13, p.168

15. Sperm with Y chromosome
Male
Egg with X sex chromosome
Female
Fertilized by
Fertilized by
Sperm with Y chromosome
Sperm with X chromosome
Genetic
sex
Embryo with XY sex chromosomes
Embryo with XX sex chromosomes
FIGURE 7.13 The major pathways of sexual differentiation and the stages at which genetic sex, gonadal sex, and phenotypic sex are established.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-13, p.168

16. Stepped Art Fig. 7-13, p.168 Male Egg with X sex chromosome Female
Fertilized by
Fertilized by
Sperm with Y chromosome
Sperm with X chromosome
Genetic
sex
Embryo with XY sex chromosomes
Embryo with XX sex chromosomes
Sex-determining region of
the Y chromosome (SRY)
brings about development
of undifferentiated gonads
and testes
No Y chromosome, so no
SRY. With no masculinizing
influence, undifferentiated
gonads develop into ovaries
Gonadal
sex
FIGURE 7.13 The major pathways of sexual differentiation and the stages at which genetic sex, gonadal sex, and phenotypic sex are established.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-13, p.168

17. Stepped Art Fig. 7-13, p.168 Male Egg with X sex chromosome Female
Fertilized by
Fertilized by
Sperm with Y chromosome
Sperm with X chromosome
Genetic
sex
Embryo with XY sex chromosomes
Embryo with XX sex chromosomes
Sex-determining region of
the Y chromosome (SRY)
brings about development
of undifferentiated gonads
and testes
No Y chromosome, so no
SRY. With no masculinizing
influence, undifferentiated
gonads develop into ovaries
Gonadal
sex
Testes secrete masculinizing
hormones, including
testosterone, a potent androgen
No androgens secreted
FIGURE 7.13 The major pathways of sexual differentiation and the stages at which genetic sex, gonadal sex, and phenotypic sex are established.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-13, p.168

18. Stepped Art Fig. 7-13, p.168 Male Egg with X sex chromosome Female
Fertilized by
Fertilized by
Sperm with Y chromosome
Sperm with X chromosome
Genetic
sex
Embryo with XY sex chromosomes
Embryo with XX sex chromosomes
Sex-determining region of
the Y chromosome (SRY)
brings about development
of undifferentiated gonads
and testes
No Y chromosome, so no
SRY. With no masculinizing
influence, undifferentiated
gonads develop into ovaries
Gonadal
sex
Testes secrete masculinizing
hormones, including
testosterone, a potent androgen
No androgens secreted
FIGURE 7.13 The major pathways of sexual differentiation and the stages at which genetic sex, gonadal sex, and phenotypic sex are established.
In presence of testicular
hormones, undifferentiated
reproductive tract and
external genitalia develop
along male lines
With no masculinizing
hormones, undifferentiated
reproductive tract and
external genitalia develop
along female lines
Phenotypic
sex
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Stepped Art
Fig. 7-13, p.168

19. Mutations that Alter Phenotypic Sex
Hemaphrodites
Have both male and female gonads
Androgen insensitivity
XY males become phenotypic females
Pseudohermaphroditism
XY males at birth are phenotypically female; at puberty develop a male phenotype
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

20. Dosage Compensation
Equalizes the amount of X chromosome products in both sexes
In XX females an inactivated X chromosome forms a Barr body in each cell
XY males do not contain Barr bodies
Fig. 7.15
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

21. Lyon Hypothesis
One X chromosome is genetically active in the body cells; the second is inactive and tightly coiled
Either the maternal or paternal chromosome can be inactivated
Inactivation is permanent (reset in germ cells)
Inactivation of second X equalizes the activity of X linked genes in males and females
ROSENSTIEL AWARD - Mary Lyon (+ others) 2007
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

22. Cytological correlates of X-inactivation in mammals
Barr body:
Present in somatic XX nuclei
Not present in XY nuclei
In X-chromosome aneuploids, all but one X
become Barr bodies
Females Barr Bodies Active X
XX 1 1
XO 0 1
XXX 2 1
XXXX 3 1
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

23. Cytological correlates of X-inactivation in mammals
Barr body:
Present in somatic XX nuclei
Not present in XY nuclei
In X-chromosome aneuploids, all but one X
become Barr bodies
Females Barr Bodies Active X
XX 1 1
XO 0 1
XXX 2 1
XXXX 3 1
Males Barr Bodies Active X
XY 0 1
XXY 1 1
XXXY 2 1
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

24. Females Are Mosaics for X-Linked Genes
Some cells express the maternal X and others express the paternal X
Cats heterozygous for orange and black gene must carry two X chromosomes
Calico cats are always female
Fig. 7.16
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

25. Woman Heterozygous for Anhidrotic Ectodermal Dysplasia
TEM of Barr Body
Fig. 7.17
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

26. X Inactivation Center (Xic)
Contains several genes
The XIST gene causes the chromosome to become coated with XIST RNA and inactivated.
Occurs at approximately 32-cell- embryo stage
Fig. 7.18
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

27. I 1 2 II 1 2 3 4
III 1 2 3 4
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Fig. 7-19, p.174

28. or why your clone may look different from you
The cloned calico cat
or why your clone may look different from you
cc or “Carbon Copy”
Rainbow
Born Dec 22, 2001
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

29. Dosage Compensation
Mechanisms that generate the same amount of X-linked
gene product regardless of chromosome dosage
Mammals: One of two X chromosomes in the
female cell is inactivated
Drosophila: X chromosome in males generates twice
the amount of gene product when compared to females
C. elegans: Activity of genes on BOTH X chromosomes is
halved to equal activity of genes on singleX chromosome in
males.
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

30. Sex-Influenced Traits
Fig. 7.20
Expressed in males and females
Usually controlled by autosomal genes
Generally phenotypic variations are due to hormonal differences between the sexes
An example is male pattern baldness
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

31. Sex-influenced traits
Some autosomal genes govern traits that show up in
both sexes but their expression differs because of
hormonal differences
example: pattern baldness in males. b allele is recessive
in one sex and dominant in the other
Male Female
b+/b+ non-bald non-bald
b+/b bald non-bald
b/b bald bald
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

32. Sex-Limited Traits Genes that produce a phenotype in only one sex
Examples
Precocious puberty
Secondary sex characteristics
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning