VI) Sex-linked Inheritance

Human Karyotype for Sex Chromosomes

• Humans possess a total of 46 chromosomes, which are organized into 23 pairs.

• Among these, 22 pairs are referred to as autosomal chromosomes, while the remaining pair consists of the sex chromosomes, which can either be XX (female) or XY (male).

Inheritance of Sex Chromosomes

• Female parents possess two X chromosomes (XX) and can pass on either one to their offspring.

• Male parents possess one X and one Y chromosome (XY), and they contribute either the X or the Y chromosome to their offspring.

• The probability of offspring being male (XY) is 50%, while the probability of being female (XX) is also 50%.

Sex Linkage

• "Sex-linked" traits refer to genes that are located on the X or Y chromosomes.

• Females have approximately 25,000 to 40,000 loci on their X chromosomes, housing many traits and characteristics, including some disorders. This higher number allows for greater genetic variation.

• Males, on the other hand, are hemizygous for X-linked traits, meaning they have only one allele for these traits. This contributes to the higher prevalence of certain genetic disorders in males.

• Example of X-linked Trait: Color Blindness:

  • Dominant allele (A) allows for normal color vision, whereas the recessive allele (a) leads to color blindness.

  • Color blindness occurs in approximately 8% of males and 0.5% of females.

  • The probability of having a color-blind child is 25% if the child is male and 50% overall given that the mother is a carrier.

Pedigree Analysis of Sex-linked Traits

• Pedigree analysis offers a visual representation of inheritance patterns for sex-linked traits across multiple generations. This can help identify carriers and those at risk for inheriting specific genetic traits or disorders.

VII) Autosomal Recessive Conditions

• Autosomal recessive conditions are generally more common than autosomal dominant conditions due to the nature of gene expression where two copies of a recessive allele must be present for the trait to manifest.

• These conditions are also more prevalent than sex-linked recessive conditions due to the greater overall number of autosomal chromosomes available for mutation.

Examples of Autosomal Recessive Conditions:
1) Phenylketonuria (PKU):

• An inherited disorder that leads to the inability to metabolize phenylalanine, an amino acid found in many protein-containing foods.

• Without treatment, phenylalanine accumulates in the body, causing severe neurological damage and intellectual disability.

• Genetic representation is denoted as A = normal (phenotypically healthy), and a = PKU.

2) Sickle-cell Anemia:

• Caused by a mutation in the beta-globin gene, where an adenine (A) is replaced by thymine (T), leading to a change in the structure of hemoglobin.

• Individuals who are homozygous for the recessive allele (ss) produce abnormal hemoglobin that can cause red blood cells to become sickle-shaped, particularly in low oxygen conditions.

• The genotypes are represented as SS = normal hemoglobin, ss = sickle-cell hemoglobin.

3) Tay-Sachs Disease:

• A fatal genetic disorder caused by the absence of Hex-A enzyme, leading to a toxic buildup of gangliosides in neurons, ultimately affecting brain function.

• Symptoms usually present by six months of age and result in death by age 4-5 years.

  • Skipping Generations: It is important to note that autosomal recessive traits can skip generations, appearing in offspring even if the parents are phenotypically normal carriers ( Aa).

  • Inbreeding: Increased occurrence of recessive traits is observed in populations where inbreeding is common due to smaller genetic pools, raising the probability of two carriers mating.

VIII) Nondisjunction

• Nondisjunction occurs when chromosomes fail to separate properly during meiosis, leading to gametes with an abnormal number of chromosomes. This can result in various genetic disorders due to aneuploidy.

• Consequences of Nondisjunction:

  • Nondisjunction is a leading cause of miscarriage in early pregnancies.

  • Common conditions include:

    • Trisomy 21 (Down's Syndrome):

    • Occurs in about 1 in 700 births.

    • Characterized by symptoms such as intellectual disability, distinctive facial features including epicanthal folds, and a single palmar crease.

    • Trisomy 18 (Edward's Syndrome):

    • More severe than Down’s Syndrome, often leading to stillbirth or death within the first year of life.

    • Trisomy 13 (Patau Syndrome):

    • Accompanied by severe intellectual disability and physical abnormalities, with a high mortality rate within the first year.

IX) Genetic Analysis Techniques

• Amniocentesis:

  • A procedure performed on pregnant women between the 14-16 weeks of gestation, wherein amniotic fluid is extracted, and fetal cells are cultured for genetic analysis.

  • Karyotyping is typically performed on these cultured cells to identify chromosomal abnormalities.

• Chorionic Villus Sampling (CVS):

  • Can be conducted earlier in pregnancy, around 8-10 weeks gestation.

  • Involves obtaining a sample from the chorionic villi of the placenta, allowing for early detection of genetic disorders.

X) Techniques Stemming from Genetic Analyses

• In Vitro Fertilization (IVF):

  • A reproductive technology where eggs are fertilized outside the body and later implanted in the uterus.

  • Embryo testing at the 8-12 cell stage can be performed to screen for chromosomal anomalies prior to implantation, aiding in the selection of healthy embryos.

  • Ethical considerations arise, especially regarding decisions around embryo selection for rare genetic disorders, which may include creating "savior siblings" designed for organ or tissue donation to existing sick siblings.