Sex Linkage and X-Linked Inheritance Patterns CH 3 sex linkage

Chapter 3: Sex Linkage

Major Learning Objectives

• Identify and define heterogametic vs homogametic sex chromosomes.

• Recognize and predict sex-linked single-gene inheritance patterns using reciprocal crosses.

• Apply sex linkage to human inheritance.

Single Gene Inheritance on the Sex Chromosomes

Structure and Function of Sex Chromosomes

Sex chromosomes, X and Y, differ significantly in size and gene content. The X chromosome contains many more genes than the Y chromosome. Despite not being homologous, X and Y chromosomes pair during meiosis due to the pseudoautosomal regions (PAR) at their ends.

• X chromosome: Larger, gene-rich.

• Y chromosome: Smaller, contains the SRY gene responsible for male development.

• Pseudoautosomal regions (PAR): Allow pairing and recombination during meiosis.

Human Sex Chromosomes and Gender Determination

XX/XY Mode of Sex Determination

In humans, sex is determined by the combination of sex chromosomes inherited from the parents. Females are XX and males are XY.

• Female gametes (eggs): Always carry an X chromosome.

• Male gametes (sperm): Carry either an X or a Y chromosome.

• Homogametic sex: Produces gametes of one type (XX in females).

• Heterogametic sex: Produces two types of gametes (XY in males).

• Hemizygous: Males have only one copy of genes on the X chromosome.

Example: Fertilization between male and female gametes produces a 1:1 sex ratio in offspring.

Model Organism for Study of X-Linkage

Drosophila melanogaster (Fruit Fly)

Drosophila is a classic model organism for studying X-linked inheritance due to its easily observable traits and short generation time.

• Eye color in Drosophila is a well-known X-linked trait.

• Reciprocal crosses between red-eyed and white-eyed flies reveal sex-linked inheritance patterns.

Reciprocal Crosses and Sex-Linked Inheritance

Definition and Importance

A reciprocal cross involves switching the sexes of parents with respect to a particular trait to determine if inheritance is sex-dependent. Mendel's monohybrid crosses were not sex-dependent, but sex-linked traits show different results depending on the direction of the cross.

• In autosomal inheritance, reciprocal crosses yield the same results.

• In sex-linked inheritance, reciprocal crosses can yield different phenotypic ratios.

Example: Crossing a red-eyed female with a white-eyed male vs. a white-eyed female with a red-eyed male in Drosophila.

X-Linkage: Drosophila Eye Color

Thomas Hunt Morgan's Experiments

Morgan's reciprocal crosses with Drosophila demonstrated that eye color is X-linked. The F1 and F2 ratios differed from Mendelian predictions, revealing the role of sex chromosomes in inheritance.

• Cross A: Red-eyed female × White-eyed male → F1 all red-eyed; F2 shows 3:1 ratio (red:white).

• Cross B: White-eyed female × Red-eyed male → F1 all red-eyed females, all white-eyed males; F2 shows 1:1:1:1 ratio (red-eyed females, white-eyed females, red-eyed males, white-eyed males).

Key Point: Males are hemizygous for X-linked genes, so recessive traits are expressed in males even if only one copy is present.

Human X-Linked Inheritance Patterns

X-Linked Dominant and Recessive Traits

X-linked traits in humans can be dominant or recessive, affecting inheritance patterns in pedigrees.

• X-linked dominant: Affected mothers can pass the trait to both sons and daughters; affected fathers pass the trait only to daughters.

• X-linked recessive: More common in males; affected males inherit the allele from their mothers and cannot pass it to their sons.

Punnett Square for X-Linked Dominant Inheritance

Parent Genotypes	Possible Offspring
Mother: XBXb (affected), Father: XbY (unaffected)	50% affected daughters (XBXb), 50% affected sons (XBY), 50% unaffected daughters (XbXb), 50% unaffected sons (XbY)
Mother: XbXb (unaffected), Father: XBY (affected)	All daughters affected (XBXb), all sons unaffected (XbY)

Punnett Square for X-Linked Recessive Inheritance

Parent Genotypes	Possible Offspring
Mother: XbXb (carrier), Father: XBY (unaffected)	All daughters carriers (XBXb), all sons unaffected (XBY)
Mother: XBXb (carrier), Father: XBY (unaffected)	50% carrier daughters (XBXb), 50% unaffected daughters (XBXB), 50% unaffected sons (XBY), 50% affected sons (XbY)

Human Pedigree Analysis: X-Linked Recessive

Patterns in Pedigrees

X-linked recessive traits often skip generations and are more frequently observed in males. Affected males inherit the allele from their mothers, who may be carriers.

• Carrier females (XBXb) can have affected sons (XbY).

• Affected males (XbY) cannot pass the trait to their sons, but all daughters become carriers.

X-Linkage in Humans: Color Blindness

Genetic Basis and Pedigree Analysis

Color blindness is a classic example of an X-linked recessive disorder. Pedigree analysis can be used to determine the genotypes of parents and affected offspring.

• Genotypes: XB = normal vision, Xb = color blind allele.

• Carrier mothers (XBXb) can have affected sons (XbY).

• Affected males (XbY) must have inherited the allele from their mother.

Example Pedigree Table

Individual	Genotype	Phenotype
Father	XBY	Normal
Mother	XBXb	Carrier
Son	XbY	Color blind
Daughter	XBXb	Carrier

Key Terms and Concepts

• Sex-linked gene: A gene located on a sex chromosome, usually the X chromosome.

• Hemizygous: Having only one allele for a gene in a diploid organism (e.g., males for X-linked genes).

• Reciprocal cross: A cross in which the sexes of the parents are reversed for a given trait.

• Pseudoautosomal region (PAR): Region of homology between X and Y chromosomes allowing pairing during meiosis.

Equations and Ratios

• Mendelian ratio for autosomal monohybrid cross:

• $3:1$

• Sex-linked F2 ratio (Drosophila, Cross B):

• $1:1:1:1$

Summary Table: Comparison of Inheritance Patterns

Inheritance Type	Reciprocal Cross Results	Sex Dependence
Autosomal	Same ratios	No
Sex-linked (X-linked)	Different ratios	Yes

Example: Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is caused by a recessive X-linked allele. A man with this disorder must have inherited the allele from his mother and cannot pass it to his sons, but all his daughters will be carriers.

Additional info: The notes also reference the importance of using Punnett squares and pedigree analysis to predict inheritance patterns and identify carriers and affected individuals in families.