Sex Determination in Humans Chromosomal sex is determined

Sex Determination in Humans • Chromosomal sex is determined at fertilization • Sexual differences begin in the 7 th 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 Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Stepped Art Fig. 7 -12 b, p. 167

Appearance of “uncommitted” duct system of embryo at 7 weeks Y chromosome present Testes Y chromosome absent Ovaries Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Stepped Art Fig. 7 -12 b, p. 167

Appearance of “uncommitted” duct system of embryo at 7 weeks Y chromosome present Testes Y chromosome absent Ovaries Ovary Penis Testis Uterus Vagina Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Stepped Art Fig. 7 -12 b, p. 167

Appearance of structures that will give rise to external genitalia 7 weeks Y chromosome present Y chromosome absent Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Stepped Art Fig. 7 -12 c, p. 167

Appearance of structures that will give rise to external genitalia 7 weeks Y chromosome present 10 weeks Y chromosome absent 10 weeks Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Stepped Art Fig. 7 -12 c, p. 167

Appearance of structures that will give rise to external genitalia 7 weeks Y chromosome present 10 weeks Y chromosome absent 10 weeks Penis Vaginal opening Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Birth approaching Stepped Art Fig. 7 -12 c, 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

Male Egg with X sex chromosome Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Female Stepped Art Fig. 7 -13, p. 168

Male Egg with X sex chromosome Sperm with Y chromosome Fertilized by Female Sperm with X chromosome 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 Sperm with Y chromosome Fertilized by Embryo with XY sex chromosomes Fertilized by Genetic sex Female Sperm with X chromosome Embryo with XX sex chromosomes 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 Sperm with Y chromosome Fertilized by Embryo with XY sex chromosomes Sex-determining region of the Y chromosome (SRY) brings about development of undifferentiated gonads and testes Fertilized by Female Sperm with X chromosome Genetic sex Embryo with XX sex chromosomes Gonadal sex No Y chromosome, so no SRY. With no masculinizing influence, undifferentiated gonads develop into ovaries 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 Sperm with Y chromosome Fertilized by Embryo with XY sex chromosomes Sex-determining region of the Y chromosome (SRY) brings about development of undifferentiated gonads and testes Testes secrete masculinizing hormones, including testosterone, a potent androgen Fertilized by Female Sperm with X chromosome Genetic sex Embryo with XX sex chromosomes Gonadal sex No Y chromosome, so no SRY. With no masculinizing influence, undifferentiated gonads develop into ovaries No androgens secreted 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 Sperm with Y chromosome Fertilized by Embryo with XY sex chromosomes Sex-determining region of the Y chromosome (SRY) brings about development of undifferentiated gonads and testes Fertilized by Sperm with X chromosome Genetic sex Embryo with XX sex chromosomes Gonadal sex No Y chromosome, so no SRY. With no masculinizing influence, undifferentiated gonads develop into ovaries Testes secrete masculinizing hormones, including testosterone, a potent androgen In presence of testicular hormones, undifferentiated reproductive tract and external genitalia develop along male lines Female No androgens secreted Phenotypic sex With no masculinizing hormones, undifferentiated reproductive tract and external genitalia develop along female lines 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 XX XO XXXX Barr Bodies Active X 1 1 0 1 2 1 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 XX XO XXXX Barr Bodies Active X 1 1 0 1 2 1 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 -cellembryo stage Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning Fig. 7. 18

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

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 single. X chromosome in males. Chapter 7 Human Heredity by Michael Cummings © 2006 Brooks/Cole-Thomson Learning

Sex-Influenced Traits • 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 Fig. 7. 20 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 b+/b+ Male non-bald Female non-bald b+/b bald non-bald b/b 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