Sex Determination | Lucent for GK - UPSC PDF Download

Introduction

• Henking (1891) observed a distinct nuclear structure throughout the process of spermatogenesis in certain insects. He noted that 50% of the sperm acquired this structure, while the remaining 50% did not. Henking named this structure the X body but could not explain its significance. Further research by other scientists revealed that Henking's "X body" was actually a chromosome, leading to its designation as the X-chromosome.
• Subsequent investigations demonstrated that in many insects, sex determination follows the XO type mechanism. In this mechanism, all eggs carry an additional X-chromosome alongside other autosomes, while some sperm carry the X-chromosome and others do not. Fertilization by sperm carrying an X-chromosome results in female offspring, while fertilization by sperm lacking an X-chromosome leads to male offspring.
• As a result of the X-chromosome's involvement in sex determination, it was designated as the sex chromosome, while the remaining chromosomes were referred to as autosomes. The grasshopper serves as an example of the XO type of sex determination, where males possess a single X-chromosome in addition to autosomes, while females have a pair of X-chromosomes.
• These observations prompted investigations into the mechanisms of sex determination in numerous species. In several other insects and mammals, including humans, the XY type of sex determination is observed, where both males and females possess an equal number of chromosomes.
• In males, there is an X-chromosome present, while its counterpart, the Y-chromosome, is noticeably smaller. On the other hand, females possess a pair of X-chromosomes. Both males and females have the same number of autosomes. Therefore, males have autosomes plus XY, while females have autosomes plus XX. In human beings and Drosophila, males possess one X-chromosome and one Y-chromosome, while females have a pair of X-chromosomes alongside autosomes.
• In the previous discussion, we examined two types of sex determination mechanisms: XO type and XY type. However, in both cases, males produce two distinct types of gametes: (a) those with or without an X-chromosome, and (b) some gametes with an X-chromosome and some with a Y-chromosome. This type of sex determination mechanism is referred to as male heterogamety.
• In other organisms, such as birds, a different mechanism of sex determination is observed. In this case, the total number of chromosomes is the same in both males and females. However, females produce two different types of gametes based on the sex chromosomes, resulting in female heterogamety.
• To distinguish it from the previously described sex determination mechanism, the two different sex chromosomes in female birds are designated as Z and W chromosomes. In these organisms, females possess one Z and one W chromosome, while males have a pair of Z-chromosomes alongside autosomes.

Sex Determination in Humans

• It has been previously stated that humans have an XY sex determining mechanism. Among the 23 pairs of chromosomes, 22 pairs are identical in both males and females, known as autosomes. Females possess a pair of X-chromosomes, while males have one X and one Y chromosome, which determines their male characteristics. In the process of spermatogenesis in males, two types of gametes are produced. Half of the sperm carry an X-chromosome, while the other half carry a Y-chromosome along with the autosomes. On the other hand, females produce ova with only X-chromosomes. When fertilization occurs, there is an equal chance of the ovum being fertilized by either an X or Y chromosome-carrying sperm.
• If the ovum is fertilized by an X-chromosome-carrying sperm, the resulting zygote develops into a female (XX), whereas fertilization with a Y-chromosome-carrying sperm leads to the birth of a male offspring. Therefore, it is clear that the genetic composition of the sperm determines the sex of the child. Additionally, in each pregnancy, there is always a 50% probability of having either a male or female child.
• Unfortunately, in our society, women are unjustly blamed and mistreated for giving birth to female children, based on this false belief.

Genetic Disorders

Pedigree Analysis:
The concept of inherited disorders has long been prevalent in human society, based on the observance of certain characteristic features being passed down through families. After the rediscovery of Mendel's work, the analysis of trait inheritance patterns in humans began. Since controlled crosses like those possible with pea plants or other organisms are not feasible in humans, studying the family history of a specific trait provides an alternative approach. This analysis of traits across multiple generations of a family is known as pedigree analysis. In human genetics, pedigree studies serve as a powerful tool for tracing the inheritance of specific traits, abnormalities, or diseases. Each feature in an organism is controlled by genes located on DNA within the chromosomes, which carry genetic information and are transmitted unchanged from one generation to the next. However, occasional changes or alterations, known as mutations, do occur in the genetic material. Many disorders in humans have been linked to the inheritance of altered genes or chromosomes.

Mutation:
Mutation is a phenomenon that causes alterations in DNA sequences, leading to changes in an organism's genotype and phenotype. Alongside recombination, mutation is another factor contributing to DNA variation. The DNA helix is tightly coiled within each chromatid, running continuously from one end to the other. Thus, the loss (deletion) or gain (insertion/duplication) of a DNA segment results in chromosome alterations. Since genes reside on chromosomes, changes in chromosomes can lead to abnormalities or aberrations, commonly observed in cancer cells as chromosomal aberrations. Additionally, mutations can occur due to single base pair changes in DNA, known as point mutations. An example of such a mutation is sickle cell anemia. Deletions and insertions of DNA base pairs cause frame-shift mutations. Various chemical and physical factors that induce mutations, such as UV radiation, are referred to as mutagens.

Mendelian Disorders

Genetic disorders can be broadly classified into two categories: Mendelian disorders and Chromosomal disorders. Mendelian disorders are primarily caused by alterations or mutations in single genes. These disorders are inherited following the principles of inheritance that we have studied. The inheritance patterns of Mendelian disorders can be determined through pedigree analysis. Examples of common Mendelian disorders include Haemophilia, Cystic fibrosis, Sickle-cell anemia, Color blindness, Phenylketonuria, Thalassemia, and more. It is worth noting that Mendelian disorders can be either dominant or recessive, and pedigree analysis can reveal whether a particular trait is dominant or recessive. Additionally, a trait may also be linked to the sex chromosome, as is the case with haemophilia. It is evident that this X-linked recessive trait is transmitted from carrier females to male offspring.

Haemophilia:
Extensive research has been conducted on this sex-linked recessive disease, which is transmitted from unaffected carrier females to some of the male offspring. In individuals affected by this disease, a single protein involved in the blood clotting cascade is affected, leading to continuous bleeding from even minor cuts. Heterozygous females (carriers) for haemophilia can pass the disease on to their sons. The likelihood of a female developing haemophilia is extremely rare because her mother must be at least a carrier, and her father must be haemophilic (which is often not viable in the later stage of life). The family pedigree of Queen Victoria demonstrates several haemophilic descendants, as she was a carrier of the disease.

Sickle-Cell Anemia:
Sickle-cell anemia is an autosomal recessive trait that can be inherited from parents to offspring when both partners are carriers of the gene (heterozygous). The disease is controlled by a single pair of alleles, HbA and HbS. Among the three possible genotypes, only individuals homozygous for HbS (HbSHbS) exhibit the diseased phenotype. Heterozygous (HbAHbS) individuals appear unaffected but carry the disease, as there is a 50 percent chance of transmitting the mutant gene to their offspring, resulting in the sickle-cell trait. The defect is caused by the substitution of Glutamic acid (Glu) with Valine (Val) at the sixth position of the beta globin chain in the hemoglobin molecule. This amino acid substitution in the globin protein occurs due to a single base substitution at the sixth codon of the beta globin gene, changing it from GAG to GUG. Under low oxygen tension, the mutant hemoglobin molecule undergoes polymerization, leading to a change in the shape of red blood cells from biconcave discs to elongated sickle-like structures.

Phenylketonuria:
Phenylketonuria is an inborn error of metabolism that is inherited as an autosomal recessive trait. Individuals affected by this condition lack an enzyme responsible for converting the amino acid phenylalanine into tyrosine. As a result, phenylalanine accumulates in the body and is converted into phenylpyruvic acid and other byproducts. The accumulation of these substances in the brain leads to mental retardation, and they are also excreted in urine due to poor absorption by the kidneys.

Chromosomal Disorders

On the other hand, chromosomal disorders occur due to the absence, excess, or abnormal arrangement of one or more sex chromosomes. Aneuploidy, which is the gain or loss of a chromosome(s), occurs as a result of chromatid segregation failure during cell division. For example, Down's syndrome is caused by the presence of an extra copy of chromosome 21. Similarly, Turner's syndrome occurs due to the loss of an X chromosome in human females. Polyploidy, which involves an increase in a whole set of chromosomes, happens when cytokinesis fails after the telophase stage of cell division. This condition is often observed in plants. In a normal human cell, the total number of chromosomes is 46 (23 pairs), with 22 pairs being autosomes and one pair being sex chromosomes. In rare cases, an individual may have an additional copy of a chromosome or lack one member of a chromosome pair. These situations are referred to as trisomy or monosomy of a chromosome, respectively. Such conditions have serious consequences for the affected individual. Down's syndrome, Turner's syndrome, and Klinefelter's syndrome are common examples of chromosomal disorders.

Down's Syndrome:
Down's syndrome, also known as trisomy 21, is caused by the presence of an additional copy of chromosome 21. This genetic disorder was first described by Langdon Down in 1866. Individuals with Down's syndrome typically have short stature, a small round head, a furrowed tongue, and a partially open mouth. They also exhibit broad palms with a characteristic palm crease, along with delayed physical, psychomotor, and mental development.

Klinefelter's Syndrome:
Klinefelter's syndrome is a genetic disorder that occurs due to the presence of an additional copy of the X chromosome, resulting in a karyotype of 47, XXY. Individuals with this syndrome exhibit overall masculine development, but they may also display feminine characteristics such as the development of breasts (known as Gynecomastia). Additionally, individuals with Klinefelter's syndrome are typically sterile.

Turner's Syndrome:
Turner's syndrome is a disorder caused by the absence of one of the X chromosomes, resulting in a karyotype of 45, X0. Females with Turner's syndrome are sterile as their ovaries are rudimentary. They also lack other secondary sexual characteristics associated with normal development.