cmb module

1. Dr Zahid Azeem
Department of Biochemitry
AJK Medical College, Muzaffarabad

2. AutosomalDominant
1 2
4 53
7
6
8
AA aa

3. AutosomalDominant
 Presence of even one
dominant allele A gives
the phenotype
 F1 only has one possible
genotype Aa
 Crossing 3 and 4 may
give either Aa|aa, but as
7 is unaffected, it must
be aa
1 2
4 53
7
6
8
AA aa
Aa Aa aaaa
aa Aa

4. AutosomalDominant
 Crossing 5 and 6 may give
either Aa|aa, but as 7 is
affected, it must be Aa
 NOT sex-limited because it
occurs in both sexes.
 NOT sex-influenced
because the heterozygous
genotype is expressed in
the same way by both sexes
(see 4 and 5)
1 2
4 53
7
6
8
AA aa
Aa Aa aaaa
aa Aa

5. AutosomalDominant
 NOT X-linked dominant
nor recessive, if so 7
should also express the
phenotype
 NOT Y-linked as it is also
observed in females
1 2
4 53
7
6
8
AA aa
Aa Aa aaaa
aa Aa

6. AutosomalRecessive
1 2
4 53
7
6
aa AA
8

7. AutosomalRecessive
 Presence of two alleles aa
gives the phenotype
 Presence of only one
allele a will not exhibit
the phenotype
 F1 only has one possible
genotype Aa
 Crossing 3 and 4 may
give either Aa|aa, but as
7 is unaffected, it must
be Aa
1 2
4 53
7
6
aa AA
Aa Aaaa
Aa aa
Aa
8

8. Autosomal Recessive
 Crossing 5 and 6 may give
AA|Aa|aa, but as 7 is
affected, it must be only aa
 NOT sex-limited because it
occurs in both sexes.
 NOT sex-influenced
because the heterozygous
genotype is expressed in
the same way by both sexes
(see 4 and 5)
1 2
4 53
7
6
aa AA
Aa Aaaa
Aa aa
Aa
8

9. AutosomalRecessive
 NOT X-linked dominant
nor recessive, if so 5
(which is a carrier)
crossed with 6, it is not
possible for 8 to express
the phenotype
 NOT Y-linked as it is also
observed in females
1 2
4 53
7
6
aa AA
Aa Aaaa
Aa aa
Aa
8

10. AutosomalDominant Sex-Limited
1 2
4 53
7
6
8 9 10
AA aa

11. AutosomalDominant Sex-Limited
 Phenotype is male-limited
 Presence of even one
dominant allele A in males
gives the phenotype
 Females are not affected
regardless of genotype
 F1 only has 1 possible
genotype Aa
 Crossing 3 and 4 may give
either Aa|aa, but either way
7 is unaffected because it is
male-limited
1 2
4 53
7
6
8
AA aa
Aa AaAA
AA Aa
aa
9
Aa
10
aa

12. AutosomalDominant Sex-Limited
 Crossing 5 and 6 may give
either Aa|aa, but as 8 is
affected, it must be Aa
 Phenotype of 9 does not
matter because it is male-
limited
 Genotype of 10 is aa
because it is an
unaffected male
1 2
4 53
7
6
8
AA aa
Aa AaAA
AA Aa
aa
9
Aa
10
aa

13. AutosomalDominant Sex-Limited
 NOT simple dominance|
recessiveness because
females do not express
the phenotype at all
 NOT sex-influenced.
Though genders show
different phenotypes for
the same genotype, one
sex (females in this case)
are unaffected whatever
the genotype (see 7)
1 2
4 53
7
6
8
AA aa
Aa AaAA
AA Aa
aa
9
Aa
10
aa

14. AutosomalDominant Sex-Limited
 NOT X-linked
dominant|recessive
because it is not observed
in females.
 NOT Y-linked, if so 8
should not be affected as
his father isn’t
1 2
4 53
7
6
8
AA aa
Aa AaAA
AA Aa
aa
9
Aa
10
aa

15. AutosomalRecessive Sex-Limited
1 2
4 53
7
6
8 9 10
aa AA

16. AutosomalRecessive Sex-Limited
 Phenotype is male-limited
 Presence of both alleles aa
in males gives the
phenotype
 Presence of only one allele
a will not exhibit the
phenotype
 Females are not affected
regardless of genotype
 F1 only has 1 possible
genotype Aa
1 2
4 53
7
6
8 9 10
aa AA
Aa AaAA
AA aa
Aa
Aa aa

17. AutosomalRecessive Sex-Limited
 Crossing 3 and 4 may give
either Aa|aa, but either
way 7 is unaffected because
it is male-limited
 Crossing 5 and 6 may give
AA|Aa|aa. Since 8 and 10
are affected, they are aa. 7
is unaffected regardless of
genotype because it is
male-limited
1 2
4 53
7
6
8 9 10
aa AA
Aa AaAA
AA aa
Aa
Aa aa

18. AutosomalRecessive Sex-Limited
 NOT simple dominance|
recessiveness because
females do not express
the phenotype at all
 NOT sex-influenced
because the
heterozygous genotype is
expressed in the same
way by both sexes (see 4
and 5)
1 2
4 53
7
6
8 9 10
aa AA
Aa AaAA
AA aa
Aa
Aa aa

19. AutosomalRecessive Sex-Limited
 NOT X-linked
dominant|recessive
because it is not
observed in females.
 NOT Y-linked, if so 4
should be affected
1 2
4 53
7
6
8 9 10
aa AA
Aa AaAA
AA aa
Aa
Aa aa

20. Autosomal Sex-Influenced
1 2
4 53
7
6
8 9 10
AA aa

21. Autosomal Sex-Influenced
 Phenotype expression
changes between males
and females.
 For this example, trait is
dominant in males while
recessive in females.
 In males, one allele A
elicits the trait while in
females, homozygous
allele A is required for
expression
1 2
4 53
7
6
8 9 10
AA aa
Aa AaAa
AA aa
aa
Aa Aa

22. Autosomal Sex-Influenced
 Heterozygote males and
females express different
phenotypes (see 4 and 5)
 Crossing 3 and 4 may give
AA|Aa|aa, but as 7 is an
affected female, it must be
AA
 Crossing 5 and 6 may give
Aa|aa. If 8 is an unaffected
male, it must be aa while 9
being an unaffected
female, she could be Aa or
aa.
1 2
4 53
7
6
8 9 10
AA aa
Aa AaAa
AA aa
aa
Aa Aa

23. Autosomal Sex-Influenced
 Since 10 is an affected
male, he can only be Aa
 NOT simple dominance|
recessiveness because
heterozygote males and
females express different
phenotypes.
 NOT sex-limited
because it occurs in both
sexes.
1 2
4 53
7
6
8 9 10
AA aa
Aa AaAa
AA aa
aa
Aa Aa

24. Autosomal Sex-Influenced
 NOT likely to be X-
linked dominant nor
recessive
 NOT Y-linked as it is also
observed in females
1 2
4 53
7
6
8 9 10
AA aa
Aa AaAa
AA aa
aa
Aa Aa

25. X-Dominant Sex-Linked
1 2
4 53
7
6
8 9 10
XAY XX

26. X-Dominant Sex-Linked
 Alleles are found on the
X chromosome
 Males with an XA
chromosome always
expresses the phenotype
as he only can only have
one X chromosome, thus
only one copy (called
hemizygous)
1 2
4 53
7
6
8 9 10
XAY XX
XY XAXXAX
XAX XAY
XY
XAX XY

27. X-Dominant Sex-Linked
 The X chromosome of
males always come from
their mother
 A male with a
heterozygous affected
mother has a ½ chance of
also having the phenotype.
 A male with a homozygous
affected mother will always
have the phenotype.
1 2
4 53
7
6
8 9 10
XAY XX
XY XAXXAX
XAX XAY
XY
XAX XY

28. X-Dominant Sex-Linked
 A female with an affected
father will always show
the phenotype
 NOT simple dominance|
recessiveness if parents
are homozygotes. If this
is not given/assumed it
is indistinguishable.
 NOT sex-limited
because it occurs in both
sexes.
1 2
4 53
7
6
8 9 10
XAY XX
XY XAXXAX
XAX XAY
XY
XAX XY

29. X-Dominant Sex-Linked
 NOT sex-influenced. If
pattern is dominant in
males, recessive in
females (or other way
around), the pedigree is
inconsistent
 NOT Y-linked because it
is observed in females
1 2
4 53
7
6
8 9 10
XAY XX
XY XAXXAX
XAX XAY
XY
XAX XY

30. X-Recessive Sex-Linked
1 2
4 53
7
6
8 9 10
XaY XX

31. X-Recessive Sex-Linked
 Alleles are found on the
X chromosome
 Males with an XA
chromosome always
expresses the phenotype
as he only can only have
one X chromosome, thus
only one copy (called
hemizygous)
1 2
4 53
7
6
8 9 10
XaY XX
XY XaXXaXa
XaX XaY
XY
XX XY

32. X-Recessive Sex-Linked
 The X chromosome of
males always come from
their mother
 A male with an affected
mother will always also
show the phenotype.
 A female with an affected
father may or may not
have the same
phenotype
1 2
4 53
7
6
8 9 10
XaY XX
XY XaXXaXa
XaX XaY
XY
XX XY

33. X-Recessive Sex-Linked
 NOT simple dominance|
recessiveness if parents are
homozygotes. If this is not
given/assumed it is
indistinguishable.
 NOT sex-limited because it
occurs in both sexes.
 NOT sex-influenced if
parents are homozygotes.
If not, it is
indistinguishable.
 NOT Y-linked because it is
observed in females
1 2
4 53
7
6
8 9 10
XaY XX
XY XaXXaXa
XaX XaY
XY
XX XY

34. Y Sex-Linked
1 2
4 53 6
8 9 10
XY
*
XX
8

35. Y Sex-Linked
 Allele is found on the Y
chromosome
 Only males have a Y
chromosome and are
the only ones with a
chance of expressing the
trait. This is called a
HOLANDRIC trait.
 NOT simple dominance|
recessiveness
1 2
4 53 6
8 9 10
XY
*
XX
XY
*
XXXX
XY* XY
XY
XX XY
8

36. Y Sex-Linked
 NOT sex-limited
because all males with
an affected father will
always express the trait.
 NOT sex-influenced as it
is never expressed in
females.
 NOT X-linked because it
is not observed in
females
1 2
4 53 6
8 9 10
XY
*
XX
XY
*
XXXX
XY* XY
XY
XX XY
8

37. Factors complicating Pedigree
1- Delayed onset of disease
2- Multigenic inheritance
3- Genomic Imprinting
4- Environmental factors