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)
Mllerian (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. 7-12b, p.167
 Appearance of uncommitted duct
system of embryo at 7 weeks

Y chromosome present Y chromosome absent

Testes Ovaries

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

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

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

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

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
Mllerian 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
Mllerian 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 Female

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

Fertilized by Fertilized by
Sperm with Y chromosome 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 Female

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex

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

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex

Sex-determining region of
No Y chromosome, so no
the Y chromosome (SRY)
Gonadal SRY. With no masculinizing
brings about development
sex influence, undifferentiated
of undifferentiated gonads
gonads develop into ovaries
and testes

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

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex

Sex-determining region of
No Y chromosome, so no
the Y chromosome (SRY)
Gonadal SRY. With no masculinizing
brings about development
sex influence, undifferentiated
of undifferentiated gonads
gonads develop into ovaries
and testes

Testes secrete masculinizing

hormones, including No androgens secreted
testosterone, a potent androgen

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

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex

Sex-determining region of
No Y chromosome, so no
the Y chromosome (SRY)
Gonadal SRY. With no masculinizing
brings about development
sex influence, undifferentiated
of undifferentiated gonads
gonads develop into ovaries
and testes

Testes secrete masculinizing

hormones, including No androgens secreted
testosterone, a potent androgen

In presence of testicular With no masculinizing

hormones, undifferentiated hormones, undifferentiated
Phenotypic
reproductive tract and reproductive tract and
sex
external genitalia develop external genitalia develop
along male lines 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 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 Males Barr Bodies Active X
XO 0 1 XY 0 1
XXX 2 1 XXY 1 1
XXXX 3 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

 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
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

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