X-Linked Recessive Inheritance
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Transcript X-Linked Recessive Inheritance
Genes, Chromosomes, and
Human Genetics
Chapter 13
Why It Matters
Progeria
13.1 Genetic Linkage and Recombination
The principles of linkage and recombination
were determined with Drosophila
Recombination frequency can be used to map
chromosomes
Widely separated linked genes assort
independently
Chromosomes
Genes
• Sequences of nucleotides in DNA
• Arranged linearly in chromosomes
Linked Genes
Genes carried on the same chromosome
• Linked during transmission from parent to
offspring
• Inherited like single genes
• Recombination can break linkage
Drosophila melanogaster
Fruit fly
• Model organism for animal genetics
• Compared to Mendel’s peas
• Used to test linkage and recombination
Gene Symbolism
Normal alleles (wild-type)
• Usually most common allele
• Designated by “+” symbol
• Usually dominant
Wild-type
+ = red eyes
+ = normal wings
Mutant
pr = purple
vg = vestigial wings
Genetic Recombination
Alleles linked on same chromosome exchange
segments between homologous chromosomes
Exchanges occur while homologous
chromosomes pair during prophase I of meiosis
Recombination Frequency
Amount of recombination between two genes
reflects the distance between them
The greater the distance, the greater the
recombination frequency
• Greater chance of crossover between genes
Chromosome Maps
Recombination frequencies used to determine
relative locations on a chromosome
Linkage map for genes a, b, and c:
1 map unit = 1% recombination = 1 centimorgan
Recombination Occurs Often
Widely separated
linked genes often
recombine
• Seem to assort
independently
• Detected by testing
linkage to genes
between them
13.2 Sex-Linked Genes
In both humans and fruit flies, females are XX,
males are XY
Human sex determination depends on the Y
chromosome
13.2 (cont.)
Sex-linked genes were first discovered in
Drosophila
Sex-linked genes in humans are inherited as
they are in Drosophila
Inactivation of one X chromosome evens out
gene effects in mammalian females
Sex Chromosomes
Sex chromosomes determine gender
• X and Y chromosomes in many species
• XX: female
• XY: male
Other chromosomes are called autosomes
Human Sex Chromosomes
Human X chromosome
• Large (2,350 genes)
• Many X-linked genes are nonsexual traits
Human Y chromosome
• Small (few genes)
• Very few match genes on X chromosome
• Contains SRY gene
• Regulates expression of genes that trigger male
development
Sex Linkage
Female (XX): 2 copies of X-linked alleles
Male (XY): 1 copy of X-linked alleles
Only males have Y-linked alleles
Sex Linkage
Males have only one X chromosome
• One copy of a recessive allele results in
expression of the trait
Females have two X chromosomes
• Heterozygote: recessive allele hidden (carrier)
• Homozygote recessive: trait expressed
Eye Color Phenotypes in Drosophila
Normal wild-type: red eye color
Mutant: white eye color
Human Sex-Linked Genes
Pedigree chart show genotypes and phenotypes
in a family’s past generations
X-linked recessive traits more common in males
• Red-green color blindness
• Hemophilia: defective blood clotting protein
Inheritance of Hemophilia
In descendents of Queen Victoria of England
X Inactivation (1)
Dosage compensation
• In female mammals, inactivation of one X
chromosome makes the dosage of X-linked
genes the same as males
Occurs during embryonic development
X Inactivation (2)
Random inactivation of either X chromosome
Same X chromosome inactivated in all
descendents of a cell
Results in patches of cells with different active X
chromosomes
Calico Cats
Heterozygote female (no male calico cats)
Barr Body
Tightly coiled condensed X chromosome
Attached to side of nucleus
Copied during mitosis but always remains
inactive
13.3 Chromosomal Alterations That
Affect Inheritance
Most common chromosomal alterations:
deletions, duplications, translocations, and
inversions
Number of entire chromosomes may also
change
Chromosomal Alterations (1)
Deletion: broken
segment lost from
chromosome
Duplication:
broken segment
inserted into
homologous
chromosome
Chromosomal Alterations (2)
Translocation:
broken segment
attached to
nonhomologous
chromosome
Inversion: broken
segment reattached
in reversed
orientation
Nondisjunction (1)
Failure of homologous pair separation during
Meiosis I
Nondisjunction (2)
Failure of chromatid separation during
Meiosis II
Changes in Chromosome Number
Euploids
• Normal number of chromosomes
Aneuploids
• Extra or missing chromosomes
Polyploids
• Extra sets of chromosomes (triploids, tetraploids)
• Spindle fails during mitosis
Aneuploids
Abnormalities usually prevent embryo
development
Exception in humans is Down syndrome
• Three copies of chromosome 21 (trisomy 21)
• Physical and learning difficulties
• Frequency of nondisjunction increases as women
age
Polyploids
Common in plants
• Polyploids often hardier and more successful
• Source of variability in plant evolution
Uncommon in animals
• Usually has lethal effects during embryonic
development
13.4 Human Genetics and Genetic
Counseling
In autosomal recessive inheritance,
heterozygotes are carriers and homozygous
recessives are affected by the trait
In autosomal dominant inheritance, only
homozygous recessives are unaffected
13.4 (cont.)
Males are more likely to be affected by X-linked
recessive traits
Human genetic disorders can be predicted, and
many can be treated
Modes of Inheritance
Autosomal recessive inheritance
Autosomal dominant inheritance
X-linked recessive inheritance
Autosomal Recessive Inheritance
Males or females carry a recessive allele on an
autosome
Heterozygote
• Carrier
• No symptoms
Homozygote recessive
• Shows symptoms of trait
Autosomal Dominant Inheritance
Dominant gene is carried on an autosome
Homozygote dominant or heterozygote
• Show symptoms of the trait
Homozygote recessive
• Normal
X-Linked Recessive Inheritance
Recessive allele carried on X chromosome
Males
• Recessive allele on X chromosome
• Show symptoms
Females
• Heterozygous carriers, no symptoms
• Homozygous, show symptoms
Genetic Counseling
Identification of parental genotypes
• Construction of family pedigrees
• Prenatal diagnosis
Allows prospective parents to reach an informed
decision about having a child or continuing a
pregnancy
Genetic Counseling Techniques
Prenatal diagnosis tests cells for mutant alleles
or chromosomal alterations
Cells obtained from:
• Embryo
• Amniotic fluid around embryo (amniocentesis)
• Placenta (chorionic villus sampling)
Postnatal genetic screening
• Biochemical and molecular tests
13.5 Nontraditional Patterns of
Inheritance
Cytoplasmic inheritance follows the pattern of
inheritance of mitochondria or chloroplasts
In genomic imprinting, the allele inherited from
one of the parents is expressed while the other
allele is silent
Cytoplasmic Inheritance
Genes carried on DNA in mitochondria or
chloroplasts
Cytoplasmic inheritance follows the maternal
line
• Zygote’s cytoplasm originates from egg cell
Cytoplasmic Inheritance
Mutant alleles in organelle DNA
• Mendelian inheritance not followed (no
segregation by meiosis)
• Uniparental inheritance from female
Cytoplasmic Inheritance
Inheritance of variegation in Mirabalis
Genomic Imprinting
Expression of an allele is determined by the
parent that contributed it
• Only one allele (from either father or mother) is
expressed
Other allele is turned off (silenced)
• Often, result of methylation of region adjacent to
gene responsible for trait