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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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