Transcript Chapter 1 A Perspective on Human Genetics

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
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
Testes
Y chromosome absent
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
Testes
Y chromosome absent
Ovaries
Ovary
Uterus
Vagina
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Penis
Testis
Stepped Art
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
10 weeks
Y chromosome absent
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
10 weeks
Y chromosome absent
10 weeks
Penis
Vaginal
opening
Chapter 7 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Birth approaching
Birth approaching
Stepped Art
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
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
Fertilized by
Sperm with Y chromosome
Female
Fertilized by
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
Fertilized by
Fertilized by
Sperm with Y chromosome
Embryo with XY sex chromosomes
Female
Sperm with X chromosome
Genetic
sex
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
Fertilized by
Fertilized by
Sperm with Y chromosome
Embryo with XY sex chromosomes
Sex-determining region of
the Y chromosome (SRY)
brings about development
of undifferentiated gonads
and testes
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
Fertilized by
Fertilized by
Sperm with Y chromosome
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
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
Fertilized by
Fertilized by
Sperm with Y chromosome
Embryo with XY sex chromosomes
Sex-determining region of
the Y chromosome (SRY)
brings about development
of undifferentiated gonads
and testes
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
XXX
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
XXX
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 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
b+/b+
Male
non-bald
Female
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