Patterns of Single-Gene Inheritance II

Patterns of Single-Gene Inheritance

• Four basic patterns of single-gene inheritance depend on whether the phenotype is dominant or recessive and the chromosomal location of the gene locus (autosome or sex chromosome)

X-Linked Inheritance

• X-linked disorders affect males more severely than females due to hemizygosity in males and heterozygosity in females
• Females can be heterozygous or homozygous at X-linked loci, while males are never heterozygous for alleles at X-linked loci
• X inactivation leads to random inactivation of one X chromosome in females, affecting expression of X-linked genes

Mitochondrial Genome

• Mitochondrial DNA (mtDNA) is a circular chromosome located inside mitochondrial organelles, not in the nucleus
• mtDNA contains 37 genes encoding 13 polypeptides, 2 types of ribosomal RNA, and 22 transfer RNAs
• Rearrangements and point mutations in mtDNA can cause human disease, often involving the central nervous and musculoskeletal systems
• Mitochondrial genome has three unusual features: replicative segregation, homoplasmy and heteroplasmy, and maternal inheritance

Maternal Inheritance of mtDNA

• mtDNA is inherited solely from the mother due to elimination of sperm mitochondria from the embryo
• All children of a female with a mtDNA mutation will inherit the mutation, while none of the offspring of a male carrying the same mutation will inherit it

Expression of X-Linked Genes

• Recessive and dominant patterns of X-linked inheritance are distinguished based on the phenotype in heterozygous females
• X-linked "dominant" and "recessive" patterns depend on the expression of the phenotype in carriers

X-Linked Recessive Inheritance

• X-linked recessive disorders are typically expressed in all males who receive the mutated allele and only in females who are homozygous for the mutation
• X-linked recessive disorders are generally restricted to males and rarely seen among females
• Hemophilia A is a classic X-linked recessive disorder

Manifesting Heterozygotes and Unbalanced Inactivation

• Female carriers of X-linked recessive alleles may occasionally express the disease, known as manifesting heterozygotes
• Manifesting heterozygotes have been described for many X-linked recessive disorders, including color blindness and hemophilia A

Characteristics of X-Linked Recessive Inheritance

• Incidence of the trait is higher in males than females
• Heterozygous females are usually unaffected, but some may express the condition with variable severity
• The gene responsible is transmitted from an affected man through all his daughters
• Any of his daughters' sons has a 50% chance of inheriting it