Sex Determination and Inheritance

8/19/2019 Sex Determination and Inheritance

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Sex Determination

and

Inheritance Related to Sex


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Some Terminologies

• Hermaphroditism: both sexes in the sameorganism

• Monoecious: both male and female reproductive

structures in the same organism

• Dioecious: either male or female reproductive

structures in one organism


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Chromosomal Sex-Determination Systems:

Sex chromosomes and non-sex chromosomes

(autosomes)

• XX-XO system:

• XX – female

• XO – male

Example: grasshoppers

• XX-X system:

• XX – female

• XY – male

Example: some plants insects reptiles and all mammals


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Chromosomal Sex-Determination Systems

• !!-!" system:• !! – male

• !" – female

Examples: #irds sna$es butterflies some amphibiansand fishes

"hich one is the homogametic%


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Concept Chec# $

Ho% does the heterogametic sex di&&er &rom the

homogametic sex'

a& 'he heterogametic sex is male( the homogametic sex is

female&

b& )ametes of the heterogametic sex have different sex

chromosomes( gametes of homogametic sex have the

same sex chromosome&

c& )ametes of the heterogametic sex all contain a Y

chromosome&

d& )ametes of the homogametic sex all contain an X

chromosome&


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• Haplodiploidy system:

• *aploid set – male• Diploid set – female

Examples: #ees +asps

and ants


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enic Sex-Determining System

• In some plants and proto,oans sex is geneticall-determined but there are no obvious differences in the

chromosomes of males and females: there are no sex

chromosomes&

• )enic sex determination: genot-pes at one or more loci

determine the sex of an individual plant or proto,oan&

• .o sex chromosomes onl- the sex/determining genes


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n*ironmental Sex Determination

• Environmental factors :

• 0impet1s position in the stac$

• 'emperature in turtles


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Sex Determination in Drosophila melanogaster

• D& melanogaster has 2 chromosomes:

3 pairs of autosomes 4 5 par of sex chromosomes

• enic +alance system: in D. melanogaster the dosage ofX chromosomes determines sex&

6or example both XY and XO flies are phenot-picall- male&

In contrast both XX and XXY flies are phenot-picall- female&

• X : 7 ratio 8X number of X chromosomes(

7 number of haploid sets of autosomes9


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Concept Chec# ,

"hat %ill +e the sexual phenotype o& a &ruit &ly %ithXX sex chromosomes and t%o sets o&

autosomes'

a& maleb& female

c& Intersex

d& metamale


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;hromosomal sex is determined atfertili,ation

Sexual differences begin in the


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Sex Determination in Humans

'hree levels to sexual development:

– chromosomal sex: presence or absence of the Ychromosome

– gonadal sex 8primar- sex determination9: +hether the

gonads develop as testes or ovaries depends on the

presence or absence of the SRY gene usuall- found on the Y

chromsome – phenotypic sex 8secondar- sex determination9: all of the

internal and external structures develop along male or female

lines depending on +hich hormones are secreted b- the

gonads&

>henot-pic sex also has a couple of distinct s-stems: theinternal ducts and the external genitalia

'+o important times: pre/natal development and pubert-


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Chromosomal Sex Determination

"e have ?@ chromosomes: A3

pairs one set from each parent& One pair of chromosomes is the

sex chromosomes X and Y&

– the other chromosomes Bust have

numbers: 5/AA&

7 person +ith A X chromosomes

8?@XX9 is female and a person+ith an X and a Y 8?@XY9 is male&

Human karyotype: chromsomes

stained to show bands, from a male


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The ole o& Sex Chromosomes

'he X chromosome contains genetic information

essential for both sexes( at least one cop- of an X is

reCuired&

'he male/determining gene is located on the Y

chromosome& 7 single Y even in the presence of several

X still produces a male phenot-pe&

'he absence of Y results in a female phenot-pe&


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Meiosis

Reproduction involves putting one cop- of each chromosome into each sperm cell

or egg cell: the process of meiosis& So meiosis starts +ith ?@ chromosomeschooses one from each pair and puts A3 chromosomes in each sperm or egg&

– 6or males 5A the sperm get an X chromosome and the other 5A get a Y chromosome&

Sometimes meiosis goes +rong 8non/disBunction9 and a sperm or egg might get A

sex chromosomes or sex chromosomes leading people +ith ?< or ?F

chromosomes& =ore on this later&&&


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.ertili/ation

6ertili,ation means the

sperm Boins the eggcreating the ,-gote

+hich is the first cell of

the ne+ individual

person&

– A3 chromosomesfrom sperm plus A3

from the egg

restores the total of

?@ chromosomes&

– 7nd the ne+individual is no+

either ?@XX 8female9

or ?@XY 8male9


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The S ene

*o+ the Y chromosome determines sex&

'he S gene located on the Y chromosome is the

primar- determinant of sexual development&

– 'hat is if a developing embr-o has a &unctional SRY

gene in its cells it +ill develop as a male& 7nd if there is

no functional SRY the embr-o develops as female&

7lthough the SRY gene is usuall- on the Y chromosome it

occasionall- gets transferred to the X&

– this leads to ?@XX males

7lso sometimes the SRY gene is inactivated b- mutation&

– 0eading to ?@XY females 8S+-er s-ndrome9

– it is also possible to have a partiall- inactive SRY gene

leading to ambiguous genitalia


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– regions on Y chromosome that sharehomolog- +ith regions on the X

chromosome

– s-napse and recombine +ith it during

meiosis

– >resence of such a pairing region is

critical to segregation of the X and Y

chromosomes during malegametogenesis

0seudoautosomal egions (01s)


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chromosomecontains:

– the male-speci&ic regiono& the (MS)

– a sex-determining

region o& the (S)

chromosome


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Sex Determination in Humans XX-X

SRY gene on the Y chromosome determines maleness

Turner syndrome: XO( 53 female births

2line&elter syndrome: XXY or XXXY or XXXXY or

XXYY( 55 male births

0oly-X &emales: 55 female births XXX


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"ith no masculini/ing

hormones3 undi&&erentiated

reproducti*e tract and

external genitalia de*elop

along &emale lines

.ertili/ed +y .ertili/ed +y

0henotypic

sex

onadal

sex

enetic

sexm+ryo %ith X sex chromosomes

Sex-determining region o&

the chromosome (S)

+rings a+out de*elopment

o& undi&&erentiated gonadsand testes

Testes secrete masculini/ing

hormones3 including

testosterone3 a potent androgen

4n presence o& testicular

hormones3 undi&&erentiated

reproducti*e tract and

external genitalia de*elop

along male lines

Sperm %ith X chromosome

gg %ith X sex chromosome .emale

m+ryo %ith XX sex chromosomes

5o chromosome3 so no

S6 "ith no masculini/ing

in&luence3 undi&&erentiated

gonads de*elop into o*aries

5o androgens secreted

Sperm %ith chromosome

Male


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Mutations that 1lter 0henotypic Sex

Hemaphrodites

– *ave both male and female gonads

1ndrogen insensiti*ity

– XY males become phenot-pic females

0seudohermaphroditism

–XY males at birth are phenot-picall- female(at pubert- develop a male phenot-pe


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7ariant Conditions

'he large maBorit- of people develop as either completel-

male or completel- female& *o+ever 5G or more of the

population has some variant condition& – ;hromosomal variations

– )ene mutations

– External conditions

7 fe+ important terms:

– )-necomastia: development of breasts in a male – *-pospadias: the urethra exits the male bod- at the base of the

penis instead of at the tip due to failure of the urethra to

become enclosed b- the urogenital folds&

– *ermaphrodite: a person exhibiting both male and female

characteristics

a true hermaphrodite has both testicular and ovariantissue sometimes as separate organs but more freCuentl-

as an ovotestis: a single organ +ith different parts& Her-

rare&

=ale pseudo/hermaphrodite has testes and no ovaries( a

female pseudo/hermaphrodite has ovaries and no testes&

–"orth noting: the Intersex Societ- of .orth 7merica finds theterm hermaphroditeJ offensive and prefers intersexJ&


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Chromosomal 7ariants

=eiosis the form of cell division that generates the

sperm and eggs carefull- puts exactl- 5 cop- of

each chromosome pair into each cell&

Sometimes meiosis goes +rong and puts or A

copies of some chromosome into a sperm or egg

cell&

– the best example of this: Do+n s-ndrome +hich

starts +ith a sperm or egg +ith A copies ofchromosome A5&

– =aternal age effect: more freCuent in older mothers

'he sex chromosomes are Cuite tolerant of variants&

=ost common t-pes involve ?F or ?< chromosomes

'here are man- other rarer t-pes +ith ?2 or even?K chromosomes such as ?KXXXXY& Such

conditions almost al+a-s lead to serious mental

deficiencies&

The general rule: i& the is present3 the person

is internally and externally male6


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2line&elter Syndrome: 893XX

Occurs about 5 per F male births& It is the

most common t-pe of sex chromosome variant&

'he presence of the Y chromosome causes a

?


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Turner Syndrome: 83X

Onl- one X chromosome sometimes called XO&

Since there is no Y chromosome the primar-gonad is the ovar- and ?FX people are female&

7bout 5 in AF live female births&

– 5G of all spontaneous abortions 8miscarriages9 are

due to 'urner s-ndrome( about K2G of all 'urner1s

embr-os die before birth

Ovaries completel- non/functional so ?FX +omenare sterile +ith no production of sex hormones and

development of secondar- sexual characteristics at

pubert-&

Some characteristic ph-sical abnormalities: short

stature lo+ hairline +ebbed s$in at nec$& Lidne-

and circulator- s-stem problems

Often have problems +ith spatial reasoning and

mathematics& 7lso social difficulties: inabilit- to

understand others1 emotions&

;an be treated +ith gro+th hormone and estrogen&

You need # X chromosomes for

proper oarian deelopment"

46,XY females $non%functional

SRYgene& resemble 'urner(s


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893X

7bout 5 in 5 live male births& =ost XYY1s are never

detected: a ver- mild condition&

since 5K@ ne+l- discovered chromosome variants aren1t

given the discoverer1s name

It +as once thought to create h-per/aggressive males +ith a

tendenc- to+ards criminal behavior&

– Richard Spec$ the $iller of eight student nurses in 5K@@

pretended 8falsel-9 to be an XYY to obtain lenienc-&

– 7 5K@2 letter to the Lancet claimed that XYY men +ere in

prison at a rate MAF/@ times as high as the prevalence in

the general populationJ based on finding A XYY1s&

– the plot of 7liens 3 involves a prison planet for XYY1s&

XYY1s are generall- normal in appearance but +ith average

height about < cm above expected and normal build& >erhaps

acne is more common than average but this is disputed& 'he- are often more ph-sicall- active some+hat dela-ed in

emotional maturit- and have a slight increase in learning and

speech problems&

6ertile normal sex drive ver- rarel- pass A Y1s to sons&

)*+(s -ritish '. series:

He had an e/tra Y, which

made him a macho criminal0


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893XXX

7bout 5 in 5 live female births& So mild

as to be onl- rarel- detected& 7lso calledtriplo/X&

Originall- called superfemaleJ 8earl-

5K@1s9& Nrolls e-es

"idel- var-ing

s-mptoms including noneat all&

Slightl- more passive and Cuiet as babies

less assertive dela-ed motor and linguistic

s$ills& Dela-ed emotional maturit- and

social s$ills& Some have slightl- decreasedintelligence and learning difficulties&

0o+er bac$ problems are common&

6ertilit- normal don1t generall- pass A X1s

to children&


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Mosaics and

Chimeras #oth terms refer to people +ho have A different chromosome

sets in different cells& 6or example a ?@XX?


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ene Mutations

'he variants up to no+ all involve +hole chromosomes +hich have lots of

genes on them& 'he effects of changing the dosage of man- genes tend

to be +idespread but mild& 8or completel- lethal as +ith most non/sex

chromosomes9&

.o+ +e are going to loo$ at several gene mutations& In these cases onl-

one gene is affected but it is completel- $noc$ed out& 'his can lead to

large effects but limited to a fe+ subs-stems in the bod-&

Rates are different: for chromosome changes about 5 in 5 births is a

t-pical freCuenc-& 6or gene mutations each parent needs to contribute a

mutated cop- of the gene so rates are usuall- 5 in 5 births or less&

Inheritance is also a factor here: most chromosomal variants are

spontaneous events and don1t run in families& )ene mutations are usuall-inherited variants: there is often a famil-communit- histor- of the variant

t-pe&

– .e+ mutations do occur spontaneousl- but it1s rare& =ost gene variants are

inherited from the parents&


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-alpha eductase De&iciency (-

1D) F/alpha reductase is the en,-me that converts testosterone

into D*'& If both copies of the gene that ma$es this en,-meare defective the person has F/7RD&

– Recall that D*' is responsible for the development of

male external genitalia

7t birth people +ith F/7RD have undescended testes and

male ducts 8+ith no female ducts9 but genitalia that appear

some+here bet+een female and ambiguous including a a

ver- small penis +ith h-pospadias 8+hich appears to be an

enlarged clitoris9 and a short vagina& Often raised as girls

7t pubert- the increase in testosterone is large enough that

some D*' gets made and the- develop a male appearance:

the testes descend the penis enlarges facial hair appears

the voice deepens muscles develop&

0arge group in the Dominican Republic: ma-be 5 in K men&;alled )uevedoces a corruption of huevos a los doceJ

8eggs//testicles/ at age 5A9& Raised as girls the- easil-

s+itch to the male role&

– Other groups found in =alta Pordan >a$istan .e+

)uinea

1lso, a character on the '. show Nip and Tuck has this condition


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ue*odoces Case


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1ndrogen 4nsensiti*ity

Incidence about 5 in A births

Qsed to be called testicular femini,ationJ& ?@XY +ith normal8undescended9 testes& 'he testes secrete testosterone but the cells

lac$ a receptor for it& .o receptor no response to the hormone&

;omplete androgen insensitivit- ;7IS&

7s a result the male ducts 8vas deferens epidid-mus seminal

vesicles9 are not present& *o+ever the testes secrete =IS +hich

causes the female ducts 8uterus fallopian tubes upper vagina9 to

degenerate&

External genitalia develop as male if D*' is present but

testosterone and D*' use the same receptor& So female

external genitalia including the lo+er A3 of the vagina&

7t pubert- the testes again secrete testosterone& 'he en,-me

aromatase converts it into estradiol& 'hus female secondar- sexual

characteristics develop& Often voluptuousl- feminineJ& .o

menstruation of course: no ovaries and no uterus& >ubic and armpit

hair is usuall- scant or absent&

– Occasionall- the undescended testes can become cancerous so the-

are often surgicall- removed after pubert- is complete 8so as to get

normal female development9&


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0artial 1ndrogen 4nsensiti*ity

Sometimes the testosterone receptors +or$

inefficientl- due to less drastic mutations than in

;7IS& In these cases the bod- cells respond in a

variable manner to testosterone leading a a +ide

variet- of ambiguous genitalia& >7IS partial

androgen insensitivit-& 7lso called Reifenstein

s-ndrome&

– there is also mild androgen insensitivit- 8=7IS9

+hich leads to completel- male appearanceinternall- and externall- but +ith some impairment

of masculini,ation at pubert-&

Hariable s-mptoms: can be predominantl- male

8+ith h-pospadia abnormal scrotum small penis9

predominantl- female 8+ith enlarged clitoris fused

labia separate vaginal and urethral openings9 or

ambiguous genitalia 8microphallus//less than 5 cmlong9 labia/li$e scrotum h-pospadia

g-necomastia&

Similar variabilit- in male internal ducts( females

ducts are usuall- absent due to =IS secretion&

Sometimes people +ith >7IS change gender

identit- after pubert- in either direction&


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Congenital 1drenal Hyperplasia

'he adrenal glands sit on top of the $idne-s and secrete a

variet- of steroid hormones including cortisone 8stress

response9 aldosterone 8salt balance9 and androgens 8male sexhormones9&

Steroid hormones are made from cholesterol through a series

of biochemical steps& 7n- one of these steps can be inactivated

b- mutation& *o+ever about KFG of ;7* cases involve

defects in the en,-me ,$-hydroxylase&

A5/h-drox-lase is needed to ma$e cortisol and aldosterone 8but

not androgens9& ;ortisol is secreted in response to the pituitar-hormone 7;'* in a feedbac$ loop& So if there isn1t enough

cortisol being made more 7;'* is made and this causes the

adrenal gland to gro+ larger 8h-perplasia9&

7nd all of those steroid molecules that +ere destined to

become cortisol and aldosterone get diverted into male sex

hormones 8androstendione and testosterone9 +hich don1t need

the A5/h-drox-lase&

Her- little effect on male fetus +hich is alread- ma$ing

testosterone except that after birth the lac$ of salt regulation

can lead to death from excess salt secretion 8salt-%asting9&


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C1H

6emale fetuses +ith A5/h-droxlase deficienc- have

some problems due to the flood of androgens released

b- the adrenal gland& 'he ovaries are normal and the

female 8=ullerian9 ducts are also normal 8since no =IS is

made9&

=ain effects are on the external genitalia: enlarged

clitoris sometimes +ith an enclosed urethra 8i&e& li$e the

penis9 labia can fuse and become scrotum/li$e vaginal

opening can be partl- or completel- closed&

7ppearance at birth varies a lot& Some appear to be

normal male +ith undescended 8because non/existent9

testes& *o+ever the chromosomes are XX the gonads

are ovaries and the uterus and fallopian tubes are

usuall- intact&

.ormall- ver- little androgen is made in childhood& ;7*

causes excess androgens throughout life leading to

rapid gro+th but an earl- closure of the bone gro+th

plates: a ver- short adult& 7lso: earl- pubert- +ithmenstrual problems 8and poor sperm production in

males9&

'he other hormones aldosterone and cortisol need to

be replaced& 'he cortisol replacement calms the 7;'*

activit- leading to less androgen production&

21H is the most fre3uent cause

of non%standard genitals ingenetically female $XX& children"


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Some n*ironmental Causes

0rogestin-induced *irili/ation& >rogestin +as used to prevent

miscarriages in the 5KF1s and @1s& Related to this is the use of androgens

to treat endometriosis during that time period and occasional accidental use

of androgens& 5@ $no+n cases&

– XX fetuses develop as normal females +ith functioning ovaries but the- ma-

develop some male secondar- characteristics and often have enlarged clitorises&Effects are ver- similar to ;7*&

.reemartin: usuall- seen in cattle: female and male t+ins +ith testosterone

from male lea$ing over to the female due to a shared placenta& .ormal

female appearance but undeveloped ovaries and masculini,ed behavior&

Rare or un$no+n in humans&

– 7ldous *uxle-1s boo$ #rave .e+ "orld has human freemartins created

b- hormone treatment of fetuses&


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Mammals: ne of two X chromosomes in the

female cell is inactiated

Drosophila: X chromosome in males generates twice

the amount of gene product when compared to females

Dosage Compensation

5echanisms that generate the same amount of X%linked

gene product regardless of chromosome dosage

C. elegans: Activity of genes on BOTH X chromosomes is

halved to equal activity of genes on singleX chromosome in

males.


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C t l i l l t f X i ti ti i l


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Cytological correlates of X-inactivation in mammals

-arr body:

7resent in somatic XX nuclei

8ot present in XY nuclei

9n X%chromosome aneuploids, all but one X

become -arr bodiesemales -arr -odies 1ctie X

XX ) )

X )

XXX # )

XXXX ; )

5ales -arr -odies 1ctie X

XY )

XXY ) )

XXXY # )


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.emales 1re Mosaics &or X-


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.ig6 96$9

"oman *etero,-gous for

7nhidrotic Ectodermal

D-splasia

E= of #arr #od-


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X 4nacti*ation Center (Xic)

;ontains several genes

'he XIST gene causesthe chromosome tobecome coated +ith XIST

R.7 and inactivated& Occurs at approximatel-

3A/cell/ embr-o stage

6ig&


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86, Sex-


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X-


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"hat is a sex-in&luenced trait'

1 sex-in&luenced trait is controlled +y a pair o&alleles &ound on the autosomes6 (5ot on sexchromosomes)

4ts expression is in&luenced +y gender

(presence o& hormones such as: estrogen3

progesterone3 testosterone3 etc6)6

Sex-in&luenced traits *ary in the degree o& the

phenotypic expression6


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xample: 0attern ;aldness

4t can occur in +oth males and &emales3

+ut is in&luenced +y the hormone

testosterone6

Th +i ti & ll l l d t di&& t


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The com+ination o& alleles lead to di&&erent

phenotypic expressions depending on gender6

"hat is the pro+a+ility that you %ill +e +ald i& your &ather is


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"hat is the pro+a+ility that you %ill +e +ald i& your &ather is

homo/ygous and +alding3 and your mother is homo/ygous

and not +alding' 6ather #1#1 x =other ##

7ll offspring are ##1

If -ou are male then -ou +ill

be bald&

If -ou are female then -ou +ill not be bald&


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1ctually3 4t=s not that simple>

=an- human traits are controlled b-

several different alleles and environmentalfactors& 'hese traits are pol-genicsuch as height& 87ctuall- the man atthe right is a pituitar- giant at


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1nother xample: Singing *oice

'he genot-pe that causes males to have atenor voice 8highest male singing voice9 causes

females to have a contralto voice 8the deepest

female singing voice9&

'he genot-pe that causes males

to have deep bass voices is thesame genot-pe that causes females

to have high soprano voices&

0 # l


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0eacoc# plumage

'he plumage of a male peacoc$ is highl-

decorated and colored +hile the plumage of afemale peahen is dull b- comparison&

1 i t & # & th


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1 *ariety o& peacoc# &eathers


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;hapter < Human

Heredity b- =ichael

Sex-4n&luenced Traits

Expressed in males andfemales

Qsuall- controlled b-autosomal genes

)enerall- phenot-picvariations are due tohormonal differencesbet+een the sexes

7n example is malepattern baldness

6ig&


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Sex-recocious pubert-

– Secondar- sex characteristics

Documents

Sex Determination and Inheritance