Article

Gender and the Genome

2018, Vol. 2(1) 16-26
Inheritance of Chromosomes, Sex ª The Author(s) 2018
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Determination, and the Human DOI: 10.1177/2470289718787131
journals.sagepub.com/home/gng
Genome: A New Paradigm

Nirmalchandra K. Shetty1

Abstract
Who is the determining factor for the sex of the offspring—mother, father, or both parents? This fundamental hypothesis proposes a
new model of sex determination, challenging the existing dogma that the male Y chromosome of the father is the sole determinant of
the sex of the offspring. According to modern science, the 3 X chromosomes (male XY and female XX) are assumed to be similar,
and the sex of the offspring is determined after the zygote is formed. In contrast to this, the new hypothesis based on theoretical
research proposes that the 3 X chromosomes can be differentiated, based on the presence of Barr bodies. The first X in female XX
chromosomes and X in male XY chromosomes are similar as they lack Barr body and are hereby denoted as ‘X’ and referred to as
ancestral chromosomes. The second X chromosome in the female cells which is a Barr body, denoted as X, is different. This X
chromosome along with the Y chromosome are referred to as parental chromosomes. Sperm with a Y chromosome can only fuse
with an ovum containing the ‘X’ chromosome. Similarly, sperm with the ‘X’ chromosome can only fuse with an ovum containing the
X chromosome. Cell biology models of gametogenesis and fertilization were simulated with the new hypothesis model and assessed.
Only chromosomes that participated in recombination could unite to form the zygote. This resulted in a paradigm shift in our
understanding of sex determination, as both parents were found to be equally responsible for determining the sex of the offspring.
The gender of the offspring is determined during the prezygotic stage itself and is dependent on natural selection. A new dimension
has been given to inheritance of chromosomes. This new model also presents a new nomenclature for pedigree charts. This work of
serendipity may contribute to future research in cell biology, gender studies, genome analysis, and genetic disorders including cancer.

Keywords
chromosomes, meiosis, sex determination, gender, genome, heredity.

Introduction In the ancient traditional view, the mother was believed to

Against the backdrop of worldwide research on the human
genome, this fundamental hypothesis gives a new dimension
to inheritance of chromosomes and sex determination.1,2 The
hypothesis is based on innovative theoretical research.
Human cells contain 46 chromosomes, which include 44 auto-
somes and 2 sex chromosomes, namely, 46, XX (female) or 46,
XY (male). In cell biology, the 2 X sex chromosomes in female
cell and the single X chromosome in male cell were assumed to be
similar; only the Y chromosome was thought to be different.3
However, the Barr body, which plays a significant role in differ-
entiating the 3 X chromosomes, is an important factor to consider.
The Barr body has been observed in the nuclei of female cells only
and not in male cells.4 This clearly indicates that the X sex chro-
mosomes in female and male cells have some differences.
be responsible for not only conceiving the offspring but also its
sex. This was replaced by the modern science view that the
father contributes the determining factor, based on observation
of sex chromosomes after zygote formation. During the ferti-
lization process, there are 2 possibilities. (1) If a spermatozoon
with an X chromosome fuses with the ovum, the offspring
would be a female (46, XX). (2) If a spermatozoon with Y
chromosome fuses with the ovum, the offspring would be male
(46, XY). The Y chromosome was therefore thought to be a
powerful determinant. The presence of Y chromosome was
necessary for the birth of a male (XY) offspring, and its
absence resulted in a female (XX) offspring.5
1
Shri Krishna Research Centre, Mumbai, Maharashtra, India

Who Is the Determining Factor for the Sex Corresponding Author:

of the Offspring? Nirmalchandra K. Shetty, Shri Krishna Research Centre, 44/1311 MIG Adarsh
Nagar, Worli, Mumbai, Maharashtra 400030, India.
(1) Mother, (2) father, or (3) both parents? Email: shrikrishna.rc@gmail.com
Shetty
According to the new hypothesis presented here, both par-
ents are equal determinants of the sex of the offspring. The
Barr body plays an important role in differentiating between
the 2 X chromosomes in female cells and the X chromosome
in male cells. The sex of the offspring depends on viable
combinations of specific sex chromosomes: the ancestral
‘X’ of the father or mother combined with the parental X/Y
from the mother/father, respectively, during the fertilization
process prior to the formation of zygote—a paradigm shift
from the idea that the father’s Y chromosome is the determin-
ing factor.6
The master blueprint that directs all cells in the body during
embryogenesis can be found in the DNA of the diploid set of
chromosomes present in the zygote, with the exception of any
subsequent changes caused by mutation and epigenetics.7,8
Current research data on the dynamics and behavior of sex
chromosomes prior to formation of the zygote are limited.
However, this hypothesis attempts to explain it theoretically.
This new hypothesis considers the possibility that the sex of the
offspring is predetermined during the process of fertilization,
prior to zygote formation.9,10
This new and innovative concept of categorizing sex chro-
mosomes as “ancestral” and “parental” was applied to cell
biology models of gametogenesis and fertilization. It resulted
in a fundamental new model, which depicts a novel pattern of
chromosomal inheritance. A new nomenclature for pedigree
charts was also developed based on this hypothesis. However,
further research is required to easily identify the chromosomes
inherited from each parent.
This fundamental hypothesis may open new perspectives
for understanding meiosis, sex determination, genetics, and
heredity. It throws new light on some observations, such as
the release of the primary polar body, the secondary polar
body, aneuploidy, X inactivation, X-linked inheritance, and
heredity.11
Materials and Methods
This theoretical research was carried out with the objective to
investigate prevailing dogma that the presence or absence of
the father’s Y chromosome in the cell determines the sex of the
offspring.12 Modern concepts state that the male and female X
chromosomes are similar and ignore the presence and absence
of Barr bodies. This new hypothesis has been created around
the possibility that the presence (and absence) of Barr body
plays a major role in determining the sex of offspring. It was
important to explore the possibility of differentiating between
the 3 X chromosomes and to evaluate any effects that may be
visible if the difference is evident.
The New Fundamental Hypothesis Elucidated By
Theoretical Research
The 3 X chromosomes were viewed from a different perspec-
tive. The central crux of this hypothesis is built around differ-
entiating between the 3 X chromosomes. The Barr body (sex
17
chromatin body) has been observed in the nuclei of female cells
only and not in male cells.13 If more than one X chromosome is
present in the nucleus, all but one X chromosome will be con-
verted into Barr bodies.14 This indicates that the XX in female
cells and the X in male cells, which were assumed to be similar,
may be different.
The 3 X chromosomes (in XX and XY) were differentiated
based on the presence or absence of the Barr body. Differences
in the X chromosomes were evident. Only one X sex chromo-
some in female cells and the single X sex chromosome in male
cells (denoted as ‘X’ and depicted as first of the 2 sex chromo-
somes) are similar, as they do not have Barr bodies. The other
X chromosome in the female, which is a Barr body (denoted as
X), is different.
Female: ‘X’ X Male: ‘X’ Y
The ‘X’ chromosome present in both female and male cells
are assumed to be ancestral (with þve charge), as the cells are
polar.15 In contrast, the Barr body X chromosome in the
female cell and Y chromosome in the male cell are assumed
to be parental (with a ve charge) and are represented as
follows:
1. ‘X’ chromosome (no Barr body): ancestral (þve) chro-
mosome in both mother and father;
2. X chromosome (with Barr body): parental (ve) chro-
mosome of mother;
3. Y chromosome: parental (ve) chromosome of father.
Meiosis, Fertilization and the New Hypothesis
The concept differentiating sex chromosomes as ancestral and
parental was substantiated by simulation of cell biology models
of gametogenesis and fertilization with the fundamental
hypothesis models.
In the cell biology model (Figure 1), during gametogenesis
of the 4 haploid gametes released, only 2 of them take part in
genetic recombination during meiosis I, whereas the other 2
gametes do not undergo genetic recombination.16
In the new model of gametogenesis (Figure 2), the sex chro-
mosomes were differentiated as ancestral sex chromosomes
and parental sex chromosomes. The 4 gametes released during
gametogenesis are depicted as follows:
Gamete—1: ancestral ‘X’ (þve) no Barr body: inactive
(no recombination)
Gamete—2: ancestral ‘X’ (þve) no Barr body: active
(participated in recombination)
Gamete—3: parental X (ve) with Barr body or Y (ve):
active (participated in recombination)
Gamete—4: parental X (ve) with Barr body or Y (ve):
inactive (no recombination)
According to the new hypothesis, only gametes that have
taken part in genetic recombination (chiasma) during game-
togenesis are capable of taking part in fertilization. The other
18
Figure 1. Cell biology model—gametogenesis. The 2 sex chromosomes in the primary gametocyte represent sex chromosomes acquired from
the mother (blue) and the father (red). The 4 haploid gametes released post recombination are depicted.
2 gametes that have not taken part in genetic recombination
are assumed to remain inactive and do not take part in ferti-
lization,17,18 as they would carry the same genes as that of the
parent.
Having arrived at this fundamental model through the appli-
cation of this concept of ancestral and parental chromosomes,
cell biology models of spermatogenesis (Figure 3A), oogenesis
(Figure 3B), and fertilization (Figure 3C) were simulated with
the new fundamental hypothesis models of spermatogenesis
(Figure 4A), oogenesis (Figure 4B), and fertilization (Figure
4C) respectively.
Cell Biology Models of Spermatogenesis, Oogenesis,
and Fertilization
The existing models presented in Figure 3 served as the basis
for developing new hypothesis models.
Spermatogenesis (Figure 3A): Spermatocytes give rise to 4
spermatids, 2 of which have X sex chromosome and the other 2
spermatids have Y sex chromosome. Only 2 of the 4 spermatids
participate in genetic recombination during meiosis I.
Oogenesis (Figure 3B): As the 4 gametes are not differ-
entiated, it is assumed that any 2 gametes can form the
secondary oocyte resulting in an ovum with only one X
chromosome.
Fertilization (Figure 3C): During fertilization, any of the 4
haploid spermatozoa can penetrate the ovum and fuse with the
X sex chromosome to form the zygote. The sex of the offspring
Gender and the Genome 2(1)
is decided based on whether the spermatozoon with the X or Y
chromosome unites with the X sex chromosome in the ovum to
form the zygote; resulting in female (XX) or male (XY)
offspring.4,6
Results
The cell biology models of spermatogenesis, oogenesis, and
fertilization were simulated after differentiating sex chromo-
somes as ancestral and parental in the new model (Figure 4).
They were systematically analyzed theoretically, and the find-
ings were presented as follows.
New Models of Spermatogenesis, Oogenesis,
and Fertilization
Spermatogenesis. The different stages of spermatogenesis in
meiosis I and II, including recombination, results in the release
of 4 haploid spermatids, as shown in Figure 4A. Only the 2
spermatids that have taken part in genetic recombination during
meiosis I, that is, the ancestral ‘X’ chromosome and parental Y
chromosome, are capable of taking part in the fertilization
process. The other 2 spermatids, the ‘X’ and Y that have not
taken part in recombination, will be inactive and cannot take
part in the fertilization process.
Oogenesis. The different stages of oogenesis, in meiosis I and
II, including chiasma, are depicted in (Figure 4B). The large
secondary oocyte (2n) has 2 sex chromosomes that have
Shetty 19

Figure 2. New model—gametogenesis. The 2 sex chromosomes in the primary gametocyte represents sex chromosomes acquired from each
parent. The sex chromosomes have been differentiated as ancestral and parental. The sex chromosome (red) represents ancestral ‘X’
chromosome with no Barr body in both male and female cells, and the sex chromosome (blue) represents parental Y chromosome in male or
parental X chromosome (with Barr body) in female, depicted as X/Y. Only the 2 gametes that undergo genetic recombination during meiosis I
(combination of red and blue) are active. The other 2 gametes that do not participate in recombination are inactive.

taken part in genetic recombination during meiosis I: the
ancestral ‘X’ chromosome and the parental X chromosome.
The other 2 sex chromosomes ‘X’ and X that have not taken
part in gene recombination are released as primary polar
bodies (2n).19
Fertilization. Only gametes that have undergone genetic recom-
bination during gametogenesis are capable of taking part in
fertilization (Figure 4C). Thus, the sex chromosomes that can
take part in fertilization are
1. Female—ovum:
a. ‘X’ chromosome (þve) comprises a relatively
small portion of parental X (ve) of mother in the
predominant ancestral ‘X’ (þve) of father.
b. X chromosome (ve) comprises a relatively small
portion of ancestral ‘X’ (þve) of father in the pre-
dominant parental X (ve) of mother.
2. Male—spermatozoon:
a. ‘X’ chromosome (þve) comprises a relatively
small portion of parental Y (ve) of father in the
predominant ancestral ‘X’ (þve) of mother.
b. Y chromosome (ve) comprises a relatively small
portion of ancestral ‘X’ (þve) of mother in the
predominant parental Y (ve) of father.
As the ‘X’ chromosome in the ovum and ‘X’ chromosome in
the spermatozoon carry the same type of charge that is (þve),
they cannot unite and are likely to repel. Similarly, the X chro-
mosome in the ovum and Y chromosome in the spermatozoon
that carry the same type of charge, that is ve, too cannot unite
and are likely to repel.
Thus, only 2 viable combination exist for the sex chromo-
somes during fertilization to form the zygote:
1. Spermatozoon carrying ancestral ‘X’ (þve) can com-
bine with parental X (ve) in the ovum to form the
zygote ‘X’ X—female offspring.
2. Spermatozoon carrying parental Y (ve) can combine
with the ancestral ‘X’ (þve) in the ovum to form the
zygote ‘X’ Y—male offspring.
Depending on whether spermatozoon with ancestral ‘X’ (þve)
chromosome or parental Y (ve) chromosome penetrates the
ovum, the corresponding ancestral ‘X’ (þve) chromosome or
parental X (ve) in the ovum carrying the same charge as the
20 Gender and the Genome 2(1)

Figure 3. Cell biology model—spermatogenesis, oogenesis, and fertilization: Spermatogenesis depicts the different stages of spermatogenesis in
meiosis I and II, including chiasma, resulting in the release of 4 haploid spermatids. Oogenesis depicts the different stages of oogenesis in meiosis I
and II, including chiasma, resulting in the release of the large 20 oocyte (2n) and I polar body (2n). Fertilization: At the time of sperm penetration,
the II polar body (n) is released, and the ovum becomes haploid with only one X sex chromosome. All the 4 spermatozoa in this model are
capable of taking part in fertilization.

Figure 4. New model—spermatogenesis, oogenesis, and fertilization. The cell biology models of spermatogenesis, oogenesis, and fertilization
were simulated. The sex chromosomes have been differentiated as ancestral and parental. The sex chromosome (red) represents the ancestral
‘X’ chromosome (no Barr body); the sex chromosome (blue) represents the parental Y or parental X (with Barr body). The sex chromosomes
that have taken part in genetic recombination during meiosis I in both (A) spermatogenesis and (B) oogenesis are the ancestral ‘X’ chromosome
(blue in red zone) and parental X chromosome (red in blue zone). The same secondary oocyte in oogenesis has been depicted twice under
fertilization (C) to portray the fusion of (1) spermatozoon ‘X’ with X of ovum to form a female zygote, and (2) spermatozoon Y with ‘X’ of ovum
to form a male zygote.

spermatozoon will be released as a secondary polar body. Thus,

Sex Determining Factor
ovum and sperm with opposite charges form the zygote of male The prevailing dogma in modern science that the father is the
(‘X’Y) or female (‘X’ X) offspring. determining factor for the sex of the offspring is based on the
Shetty 21

Figure 5. Fertilization and sex determination—new model. The ancestral ‘X’ chromosomes in the ovum and spermatozoon with a þve charge
will repel each other and cannot unite. Similarly, the parental X chromosome in the ovum and the Y chromosome in the spermatozoon with a
ve charge will repel each other and cannot unite. There are only 2 possible combinations of sex chromosomes during fertilization. (1)
Ancestral ‘X’ (þve) of mother can unite only with parental Y (ve) of father to form zygote ‘X’ Y—male. (2) Ancestral ‘X’ (þve) of father can
unite only with parental X (ve) of mother to form the zygote ‘X’ X—female. In the new pattern of depicting sex chromosomes, the ancestral
‘X’ chromosome is followed by the parental X/Y sex chromosome. The sex chromosomes would be depicted as: Female: ‘X’ X Male: ‘X’ Y.

observation of sex chromosomes after the zygote is formed.20
This new model, however, is based on possible combinations of
specific sex chromosomes at the time of fertilization in the
prezygotic stage. In this model, a specific spermatozoon would
penetrate the ovum to form the zygote; this may be mutually
decided by the ovum and the spermatozoon through cell signal-
ing prior to fertilization.21,22 Thus, there is equal possibility of
a male or female offspring to be born. The sex of the offspring
is determined through natural selection in the pre-zygotic stage
itself. This is clearly depicted in Figure 5. Thus, both parents
are equally responsible for the sex of the offspring.
It was also possible to support this hypothesis by simulating
cell biology models of gametogenesis by the application of
principles of opposites Yin–Yang which is relevant to this
day.23 According to the Yin–Yang principle, every object or
phenomena in the universe consists of 2 complementary
opposites: Yin and Yang (Yin is ve and Yang þve). The
twin polarities are in an eternal conflict with each other, inter-
dependent, and cannot exist alone. Yin (ve) is passive in
nature, whereas Yang (þve) is active. Some examples of
Yin–Yang are (1) night is Yin (ve) and day is Yang (þve),
(2) female is Yin (ve) and male is Yang (þve), and (3) the
south pole of a magnet is Yin (ve) and the north pole is Yang
(þve). Another good example of Yin–Yang is seen in the
diploid set of chromosomes in the human cell (2n ¼ 46); one
member of each pair of chromosomes is of maternal origin
(Yin ve), whereas the other is of paternal origin (Yang þve).
According to Yin–Yang principles, absolute Yin or Yang
cannot exist alone, such as the North pole (Yang) and South
pole (Yin) of a magnet. This principle also applies to the sex
chromosomes where recombination does not occur.
Inheritance of Chromosomes
A novel pattern of inheritance of chromosomes has emerged
from this fundamental new model, depicted in Figure 6. Either
the ancestral ‘X’ (þve) chromosome of the mother would com-
bine only with parental Y (ve) chromosome of the father,
resulting in a male offspring (XY), or the ancestral ‘X’ (þve)
chromosome of the father would combine only with the par-
ental X (ve) chromosome of the mother, resulting in a female
offspring (XX).
Ancestral ‘X’ sex chromosome of the father always gets trans-
ferred to the daughter, and ancestral ‘X’ sex chromosome of the
mother is always transferred to the son. Similarly, the parental Y
chromosome gets transferred from father to son and the parental X
chromosome (Barr body) gets transferred from mother to daugh-
ter only. Theoretically, this shows that, both parents are equally
responsible for determining the sex of the offspring.
Fundamental Principles of the New Theory
 The sex of the offspring, which forms an important fac-
tor in evolution, depends on natural selection. Both par-
ents are equally responsible for determining the sex of
the offspring. One out of the pair of sex chromosomes
(XX or XY) in both female and male cells pertains to the
predominantly ancestral chromosome (‘X’), and the
other sex chromosome pertains to the predominantly
22
Figure 6. Inheritance of chromosomes—new hypothesis model. A
new dimension is given to inheritance of chromosomes in this new
model. This schematic diagram depicts the pattern of inheritance of
(1) Ancestral sex ‘X’ chromosomes from the mother and father and
(2) Parental X (of mother) or Y (of father) chromosomes across 5
generations (I-V) based on sex chromosome combinations that can
occur during fertilization to form the zygote. This pattern of chro-
mosomal inheritance is applicable to autosomes as well. To depict the
autosomes, sex chromosomes can represent autosomes, but the Y
sex chromosome needs to be replaced with an X autosome.
parental chromosome (X or Y), depicted as ‘X’ X
(female) and ‘X’ Y (male).
 Fertilization involves a combination of the ancestral
chromosome ‘X’ of a parent of the opposite sex to that
of the offspring, with the parental sex chromosome X or
Y of another parent of the same sex as that of the off-
spring. Thus, the ‘X’ chromosome is always transferred
to the offspring of the opposite sex (i.e., from father to
daughter or mother to son). The parental X or Y chro-
mosome is always transferred to the offspring of the
same sex (i.e., X from mother is transferred to daughter
and Y from father is transferred to son).
 Only chromosomes that have taken part in recombina-
tion during meiosis are capable of being transferred to
the offspring so as to maintain continuity of the heredi-
tary chain. The presence of the ancestral ‘X’ chromo-
some is essential for the survival of the embryo. This
pattern of inheritance of ancestral and parental chromo-
somes is also applicable to autosomes.
Gender and the Genome 2(1)
Hereditary Characteristics and Genetics:
New Nomenclature
Hereditary characteristics depend on gene recombination,
which occurs during chiasma as well as the combination of the
chromosomes of both parents during fertilization to form the
zygote, in accordance with the new pattern of inheritance of
chromosomes. Crossovers resulting in genetic recombination
may be taking place at different points on the chromosomes,
each time depending on natural factors such as time, internal
milieu such as homeostasis and epigenetic influence, and exter-
nal factors such as the environment and geographical location.
The hereditary pattern based on the combination of sex chro-
mosomes, aside from contributing to the gender of the off-
spring, may broadly appear as follows:
a. Male offspring (‘X’ Y)—Combination of ‘X’ chromo-
some, which would predominantly have ancestral char-
acteristics of the maternal side with some of the
mother’s characteristics because of recombination; and
the Y chromosome, which would predominantly have
characteristics of the father with some ancestral charac-
teristics from the paternal side.
b. Female offspring (‘X’ X)—Combination of ‘X’ chro-
mosome, which would predominantly have ancestral
characteristics from the paternal side, with some of the
father’s characteristics because of recombination; and
the X chromosome, which would predominantly have
characteristics from the mother, with some ancestral
characteristics from the maternal side.
New Nomenclature for Pedigree Charts
A new nomenclature for pedigree charts was developed
(Figure 7) based on the pattern of inheritance of ancestral and
parental chromosomes. It gives a new dimension to the inheri-
tance of hereditary traits. Of the 2 sex chromosomes, XX or
XY, the first chromosome ‘X’ represents the ancestral sex
chromosome; the second chromosome, X or Y, represents the
parental sex chromosome from the mother or father, respec-
tively. Autosomes are also differentiated in the same manner.
In pedigree charts, suffix numbers would be given in
sequential order to ancestral sex chromosomes as ‘X’1, ‘X’2,
‘X’3 and parental sex chromosomes as X1, X2, and X3 or Y1,
Y2, and Y3. It will also be essential to depict married partners in
these pedigree charts. Siblings, however, will carry one sex
chromosome from each parent; therefore, their chromosome
combinations would be easy to discern by applying this new
pattern of inheritance of chromosomes. New numbers in
sequential order would be given to the sex chromosomes of
new members joining the family through marriage.
Applying the new nomenclature for pedigree charts
(Figure 8) gives better clarity for the inheritance of hereditary
characteristics.24 It would help in genetic counseling and in
improving our understanding of how some types of consangui-
neous marriages predispose offspring to genetic disorders, such
Shetty 23

Figure 7. Pedigree charts—new nomenclature. The inheritance of sex chromosomes based on the new hypothesis is depicted in the pedigree
chart by applying the proposed new nomenclature. The ancestral ‘X’ chromosome is depicted in red and appears as the first of the 2 sex
chromosomes. The chromosomes depicted in blue refer to the parental X or Y chromosomes. Suffix numbers are to be given in sequential
order to the ancestral sex chromosomes as ‘X’1, ‘X’2, ‘X’3 and parental chromosomes as X1, X2, X3 or Y1, Y2, Y3. It is essential to depict the new
married partners with new numbers for their sex chromosomes in sequential order. This pattern of inheritance of chromosomes can also be
applied to autosomes.

as couples whose fathers are brothers or those whose mothers
are sisters. However, it is clear from Figure 8 A that 1 type of
consanguineous marriage in which the couples parents are
brother and sister, would not cause genetic disorders in the
offspring.25 The new nomenclature for pedigree charts can be
applied only after new techniques are developed to more easily
differentiate chromosomes inherited from mother and father in
the karyotypes.
Discussion
Theoretical Analysis of the New Model
1. Significance of Barr body: Presence or absence of Barr
body in the X sex chromosomes helps in differentiating
it and forms the basis for the new hypothesis.
2. Inheritance of sex chromosomes: (a) it is clear in mole-
cular biology that the Y chromosome is always trans-
ferred from father to son. Therefore, the son’s X sex
chromosome would have to be inherited from the
mother. However, as the son’s X sex chromosome does
not have Barr body, it is clear that the ancestral ‘X’
chromosome from the mother must be transferred to the
son. (b) As the Y chromosome is always transferred
from father to son, the ancestral ‘X’ sex chromosome
of the father would always be transferred to the daugh-
ter. The second sex chromosome of the daughter which
is inherited from the mother would be the parental X
chromosome (with Barr body), as the ancestral ‘X’
chromosome (without Barr body) of the mother as men-
tioned above will always be transferred to the son.
Although the 2 sex chromosomes of the mother (XX)
appear to be similar, according to this new hypothesis,
they are different and are transferred to the son or
daughter specifically as mentioned above and not at
random as is currently thought.
3. Aneuploidy: Sex chromosome aneuploidies occur rela-
tively frequently during meiosis.26
a. YO—nonviable: Presence of ancestral ‘X’ chromo-
some is essential for embryo survival, and the par-
ental X or Y chromosome may be necessary for the
expression of some specific sex characteristics. YO
does not exist because of the absence of ancestral
‘X’ sex chromosome.
b. XO—(Turners syndrome): Girls with XO chromo-
somes survive because of the presence of the ances-
tral ‘X’ chromosome inherited from the father.26
However, some female sex characteristics are
affected in patients with this syndrome: The female
is sterile and will not experience puberty. These are
attributed to the absence of the parental (mother’s)
X chromosome.27
c. XXX, XXXX, karyotypes: Normal fertile females
with mild phenotypic effects because the ancestral
‘X’ chromosome is present and parental X chromo-
somes are present in greater numbers.
d. XXY—(Klinefelter syndrome): Nonfertile male.28
Besides having the ancestral ‘X’ sex chromosome,
24 Gender and the Genome 2(1)

Figure 8. New nomenclature—pedigree charts. All individuals are identified by their sex chromosomes based on the new nomenclature for
chromosomal inheritance. Of the 2 sex chromosomes in males (XY) and females (XX), the first X chromosome is ancestral chromosome, and it is
followed by the parental X/Y chromosome. (A). Genetics in consanguineous marriages: the pattern of inheritance of chromosomes in 3 types of
consanguineous couples who are first cousins. Similar chromosomes (indicated in blue), of offspring and their grandparents are seen in the case of
offspring in A, whose grandmothers happen to be sisters, and in C, whose grandfathers happen to be brothers. However, no such similarity is noted
in B, whose grandparents are brother and sister. (B). New hypothesis model for X-linked inheritance. Affected males are depicted in blue, and carry
the affected ancestral ‘X’ chromosome of the mother. (C). New hypothesis model for dominant inheritance. Affected persons indicated in blue.
Shetty
the presence of both the parental sex chromosomes
(X and Y) may result in the expression of some sex
characteristics of both male and female.
4. X-inactivation: All but one X chromosome in female
cells are inactivated in order to compensate for the
presence of only one X chromosome in male cells, as
the Y chromosome is very small compared to the X
chromosome with regard to the number of genes it con-
tains.29 According to the new model, the presence of the
ancestral ‘X’ chromosome, inherited from the father, is
essential for the embryo to survive; therefore, the ances-
tral ‘X’ chromosome cannot be inactivated. Thus, the
inactivation is expected to take place only in the par-
ental X chromosome.
Inactivation of one of the X sex chromosome in
female cells for dosage compensation may be predeter-
mined at the time of zygote formation and not at the
time of expression of Xist gene in blastocyst stage as is
believed at present.30 The presence of Sry gene/testis-
determining factor or the germ cells that direct the
formation of the testis or absence of it are only events
that might be predetermined at the time of the formation
of the zygote itself.31
However according to Lyons hypothesis, X-
inactivation is a random phenomenon in which either of
the 2 X chromosomes in the female undergo inactivation
during early development.32 This may be attributed to
epigenetics and mutations in a few cells after the forma-
tion of the zygote. Recent studies have shown that several
genes escape X-inactivation.33 This may be required to
express parental hereditary characteristics in the female
and to balance genes present in the Y chromosome.
5. Autosomes: The inheritance pattern of ancestral chro-
mosomes and parental chromosomes is not restricted to
sex chromosomes only but to autosomes as well.34
6. Genetic recombination: An important aspect of evolu-
tion is genetic recombination, which takes place during
meiosis I; the inheritance of hereditary characteristics
depends on it. Only gametes that have undergone
genetic recombination are capable of going through the
process of fertilization to form the zygote. Other
gametes that have not participated in gene recombina-
tion are eliminated, as they would possess the same
characteristics as the parent.
7. X-linked inheritance: If the gene causing a disease such
as hemophilia is X-linked and is transferred from mother
to son with the daughters as carriers, then the pattern of
inheritance that is applicable can be explained as fol-
lows.35 The disease gets expressed in the male offspring
if the gene is present in the ancestral ‘X’ sex chromo-
some which is inherited from the mother. During recom-
bination, there is more or less 50% chance of the gene
being transferred to parental X sex chromosome. X-
linked inheritance depends on the time when recombina-
tion occurs as well as the time when fertilization has
taken place: (1) If the gene is present in the ancestral
25
‘X’ sex chromosome of the mother post recombination,
and if a male is born, it would be hemophiliac. If a female
is born, it would be normal. (2) However, at the time of
recombination, if the gene is transferred to parental X sex
chromosome of the mother and fertilization takes place
and a male baby is born, it would be normal; if a female
baby is born it would be a carrier.
Conclusion
This fundamental hypothesis portrays a novel pattern for
inheritance of ancestral and parental chromosomes, which is
applicable to both sex chromosomes and autosomes. Both par-
ents are equally responsible for the sex of the offspring, which
is predetermined at the time of fertilization, prior to the forma-
tion of the zygote. The time of recombination, along with the
time of conception of the male or female zygote, plays an
important role in the inheritance of hereditary characteristics.
The new nomenclature for pedigree charts may help for genetic
counseling. Further research is required to develop new tech-
niques for identifying chromosomes inherited from each par-
ent. This fundamental hypothesis may open new vistas for our
understanding of meiosis, fertilization, gender, and genome. It
may help future research in finding solutions to genetic disor-
ders including cancer.
Acknowledgments
I thank Prof H. Sharatchandra and Dr Satyavati M. Sirsat for construc-
tive discussions.
Declaration of Conflicting Interests
The author declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author received no financial support for the research, authorship,
and/or publication of this article.
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