Basic Chart Elements
A universal symbol system is used to construct pedigrees. Generations are designated by Roman numerals (I, II, III), and each individual within a generation is assigned an Arabic numeral.
- Square denotes a male, and circle denotes a female.
- Filled (shaded) symbol indicates an affected individual with phenotypic expression of the trait.
- Clear (unshaded) symbol corresponds to a phenotypically unaffected individual.
- Arrow always points to the proband—the individual who serves as the starting point for pedigree construction.
X-Linked Recessive Inheritance
This mode of gene transmission has clear criteria that are easy to identify when analyzing generations:
- Preponderance of affected males. Because males are hemizygous (possess only one X chromosome), the recessive gene is expressed immediately.
- Female carriers. They are heterozygous and rarely affected (only in cases of homozygosity).
- No male-to-male transmission. An affected father passes only his Y chromosome to his sons, leaving them unaffected.
- Specific "knight's move" pattern. An affected father transmits the mutant gene to all his daughters, making them obligate carriers. These phenotypically normal women then pass the condition on to their sons.
- Generation skipping. The disorder may skip a generation and reappear in subsequent ones.
Y-Linked and Maternal Inheritance
In addition to X-linked traits, other characteristic transmission patterns exist:
- Y-linked (holandric) inheritance. Only males are affected. The pathology is transmitted strictly through the male line: from an affected father to all his sons. Daughters in such families are always unaffected and are not carriers.
- Maternal (mitochondrial) inheritance. The disease occurs in both sexes but is transmitted to offspring exclusively by an affected mother. She passes the trait to absolutely all of her children. If the father is affected, all of his offspring will be unaffected because he does not transmit this genome.
Chromosomal and Genomic Disorders
Pathologies associated with changes in chromosome structure or number occur with a frequency of 6 per 1,000 live births. Most large genomic mutations (polyploidy, autosomal monosomies) are lethal.
In genetics, the severity rule applies: the larger the chromosomal imbalance, the earlier it manifests during ontogeny and the more severely physical and mental development are impaired.
Mutations are divided into:
- Complete forms: arise in gametes, and the altered karyotype is present in all cells of the body.
- Mosaic forms: arise in somatic cells during early embryogenesis, forming clones of both normal and abnormal cells.
Sex Chromosome Abnormalities: Klinefelter Syndrome
Nondisjunction of sex chromosomes leads to the formation of abnormal gametes (e.g., XX or 0). Upon fertilization, quantitative anomalies arise. Mosaicism in these pathologies is rarely observed.
A classic example is Klinefelter syndrome (most commonly the 47,XXY karyotype), occurring in 2–2.5 per 1,000 newborn males.
Clinical Manifestations:
- Tall stature and disproportionately long limbs.
- Eunuchoid body habitus and female-pattern fat distribution.
- Sparse body hair and gynecomastia.
- Hypogonadism and infertility (due to impaired spermatogenesis and decreased testosterone).
A general rule for such anomalies is an increase in the production of female sex hormones and a decrease in intellect. Furthermore, the degree of cognitive impairment correlates directly with the number of extra chromosomes (e.g., in 48,XXXY or 49,XXXXY variants).