Genetics: X-Linked Inheritance Patterns

X-Linkage

• Genes located on the X-chromosome exhibit unique inheritance patterns in human pedigrees, exemplified by red-green color blindness.

X-Linked Recessive Mutation in Humans

• Most individuals affected by rare X-linked recessive traits are male.
• Daughters of affected males can be heterozygous carriers and potentially have affected sons.
• Sisters of affected males can also have affected sons.
• Offspring of affected males are typically unaffected.

X-Linked Recessive Mutation in Humans: Hemophilia

• Pedigree charts illustrate X-linked recessive inheritance, such as hemophilia, across families, showing affected and unaffected individuals.
• Key figures in the pedigree are labeled (e.g., affected male, unaffected female, etc.).

Genetic Linkage

• Linked genes are located close together on a chromosome and tend to be inherited together during meiosis.
• Crossing over during meiosis can create recombinant chromosomes, with genes swapped.
• Recombination frequency (the likelihood of crossing over) is a measure of the genetic distance between genes.

Crossing Over Creates Recombination

• Crossing over, a process occurring during prophase I of meiosis, results in the exchange of genetic material between homologous chromosomes.
• This exchange creates recombinant chromosomes, which have new combinations of alleles.
• The overall frequency of recombinant chromosomes reflects the genetic distance between the involved genes.

Crossing Over May Not Occur in the Interval Between 2 Linked Genes

• Crossing over does not occur in every case between genes located on the same chromosome.
• Crossing over frequency between linked genes can range from 0% to 50%.

Genetic Maps

• Genetic maps depict the order and relative distances between genes on a chromosome.
• Distances are in map units, which correspond to the frequency of recombination between the genes.
• Map units follow an additive property; for example, if map units of genes w, rb, and cv are 1.5, 2, and 6.2 respectively, then the map unit between w and cv is 1.5 + 2 + 6.2 = 9.7.

Mapping Genetic Risk Factors

• Genetic risk factors can be assessed by analyzing the association between a gene mutation and a specific single nucleotide polymorphism (SNP).
• A positive association suggests the gene mutation may be close to the SNP.
• No association (a lack of relationship between a mutation and an SNP) indicates the precise location cannot be determined.

Y-Linked Genes

• Only males inherit and express Y-linked traits.
• Females do not inherit or pass on Y-linked traits.
• All sons of an affected male will also be affected.

Y Chromosome Haplotypes

• Y-chromosome haplotypes represent specific DNA sequences characteristic of a given lineage or population.
• These haplotypes can be traced across geographic regions.

Inheritance of Mitochondrial and Chloroplast DNA

• Mitochondria and chloroplasts contain their own DNA (mtDNA and cpDNA).
• These organelles' genes are inherited independently from nuclear chromosomes, most notably through the maternal line.
• Mitochondrial inheritance is maternal.

Inheritance of Mitochondrial DNA

• Both males and females can possess mitochondrial DNA mutations.
• Males cannot transmit mitochondrial DNA mutations to their offspring; only females can transmit to their offspring.
• All offspring of a mother with a mitochondrial DNA mutation will inherit the mutated gene.

mtDNA Inheritance

• mtDNA is primarily inherited from the mother.
• The inheritance pattern can be observed in family pedigrees.

Mutation

• Variations among individuals originate from mutations, which alter the genetic material (DNA).
• Mutations are inheritable changes in the genetic material.
• These alterations occur randomly and spontaneously in reproductive (germ-line) or non-reproductive (somatic) cells.

Somatic vs. Germ-Line Mutations

• Germline mutations occur in reproductive cells and are heritable.
• Somatic mutations occur in non-reproductive cells and are not heritable.
• Examples such as the BRCA1 gene can increase cancer risks if mutated.

How Do Mutations Arise?

• Mutations can arise spontaneously without environmental influences.
• Environmental factors can sometimes contribute to mutations.

How Do Mutations Occur?

• Mutations can arise due to various factors, such as X-rays, UV light, hydrogen peroxide, highly reactive chemicals, and radiation.
• Several types of DNA damage can result from these factors, including single-stranded and double-stranded breaks, and cross-linked bases.

Point Mutations

• Point mutations involve changes in a single nucleotide of a DNA sequence.
• They can lead to different outcomes, such as synonymous mutations (no amino acid change), nonsynonymous mutations (amino acid change), or nonsense mutations (stop codon formation).

Do Point Mutations Matter?

• Synonymous mutations typically do not affect the protein sequence but nonsynonymous mutations do.
• Missense and nonsense mutations both alter a protein's amino acid sequence potentially leading to a defective or non-functional protein sequence.

Sickle-Cell Anemia

• The example disease, sickle-cell anemia, demonstrates how a nonsynonymous point mutation in beta-globin affects hemoglobin structure and function.
• This change results in abnormal red blood cells (sickle cells).

Nonsense Mutations

• Nonsense mutations introduce premature stop codons into an mRNA sequence.
• These mutations truncate protein translation.

Insertions and Deletions

• Insertions and deletions add or remove nucleotides from a DNA sequence.
• These alterations can cause frameshift mutations disrupting the reading frame of the resulting mRNA sequence.

Frameshift Mutations

• Frameshift mutations are nucleotide insertions or deletions that are not multiples of three nucleotides.
• These mutations cause a shift in the reading frame, leading to changes in the amino acid sequence of the corresponding protein.

Genetic Variation

• Genetic variation describes differences in genetic material among individuals within a population, a genetic diversity.
• Genetic variation stems fundamentally from mutations.

Polymorphisms

• Polymorphisms are common genetic differences among individuals.
• Single nucleotide polymorphisms (SNP) are instances of polymorphisms that involve differences in a single nucleotide position within a DNA sequence.

Genotype-by-Environment Interactions

• Interactions between genotype and environment affect phenotype expression.
• Variations between individuals can be explained by a combination of genetic factors and environmental influences.

Complex Traits

• Complex traits are influenced by multiple genes and environmental variables.
• Height and blood pressure are examples of quantitative traits exhibiting continuous variation.

Complex Traits Influenced by the Environment

• Environmental factors play a critical role in determining the expression of complex traits.
• Amount of sunshine, water, nutrients, and high salt intake are examples of environmental factors.

Complex Traits Influenced by Multiple Genes

• Multiple genes influence a complex traits.
• Different variants of a gene may lead to different variations in the final trait.

VNTR (Variable Number of Tandem Repeats)

• VNTRs are repeated DNA sequences.
• Individuals can have differing numbers of VNTRs at specific locations.
• VNTR is a technique used in DNA fingerprinting to distinguish individuals based on unique banding patterns.

VNTR = DNA Fingerprinting

• VNTR analysis generates unique banding patterns for individuals for forensic or identification purposes.

Relevant Reading

• The readings are listed at the start of each section, with page numbers if provided.

Test your knowledge on X-linked inheritance patterns and their characteristics. Explore key concepts such as carrier status, crossing over, and genetic linkage. This quiz covers various aspects of X-linked recessive and dominant disorders.