Passage
Mitochondria are thought to have been independent bacterial organisms that were engulfed and integrated into eukaryotic cells approximately two billion years ago. Most of the mitochondrial genome was lost or transferred into the large central genome of the eukaryotic nucleus, leaving only a residual genome within each mitochondrion.Because multiple mitochondria are found in the cell, mitochondrial DNA (mtDNA) mutations result in a condition known as heteroplasmy, or the intracellular mixture of wild-type mtDNA and mutant mtDNA. Just as the cellular ratio of wild-type to mutant mtDNA varies, the overall mtDNA content within a tissue or organ is also highly variable. For this reason, disease-causing mutant mtDNA manifests phenotypically only when the majority of mitochondria within a given tissue express the deleterious allele. In addition, the variability in mtDNA content makes it possible for individuals with the same mitochondrial mutation to display drastically different clinical symptoms.To investigate how heteroplasmy influences disease manifestation, researchers analyzed an A to G substitution at nucleotide 3243 in the tRNA^leu gene of mtDNA. This mutation has been associated with hereditary hearing loss, diabetes mellitus, and a syndrome characterized by mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes.Family members who were confirmed to have the A3243G mutation were tested using an audiometry examination to assess hearing impairment, as shown in Table 1. The subjects carried no other genetic mutations known to cause hearing loss.Table 1 Audiometry Results From Family Members with the A3243G Mutation
The blood samples of these subjects were collected, and the 3243 region of the tRNA^leu gene was amplified via standard PCR. The PCR products were subsequently treated with the restriction enzyme ApaI and visualized on a PAGE gel. The normal undigested PCR product is 161 bp in length, but the PCR product amplified from the mutant A3243G is digested into two fragments by ApaI.
Figure 1 PAGE visualization of PCR products following ApaI digestion
Adapted from Hadjivasiliou Z, Pomiankowski A, Seymour RM, Lane N. Selection for mitonuclear co-adaptation could favour the evolution of two sexes. Proc Biol Sci. 2012;279(1734) :1865-72.
-Which of the following would be true regarding the inheritance of the A3243G mutation? (Note: Assume affected individuals inherited the mutation.)

Question

Passage
Mitochondria are thought to have been independent bacterial organisms that were engulfed and integrated into eukaryotic cells approximately two billion years ago. Most of the mitochondrial genome was lost or transferred into the large central genome of the eukaryotic nucleus, leaving only a residual genome within each mitochondrion.Because multiple mitochondria are found in the cell, mitochondrial DNA (mtDNA) mutations result in a condition known as heteroplasmy, or the intracellular mixture of wild-type mtDNA and mutant mtDNA. Just as the cellular ratio of wild-type to mutant mtDNA varies, the overall mtDNA content within a tissue or organ is also highly variable. For this reason, disease-causing mutant mtDNA manifests phenotypically only when the majority of mitochondria within a given tissue express the deleterious allele. In addition, the variability in mtDNA content makes it possible for individuals with the same mitochondrial mutation to display drastically different clinical symptoms.To investigate how heteroplasmy influences disease manifestation, researchers analyzed an A to G substitution at nucleotide 3243 in the tRNA^leu gene of mtDNA. This mutation has been associated with hereditary hearing loss, diabetes mellitus, and a syndrome characterized by mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes.Family members who were confirmed to have the A3243G mutation were tested using an audiometry examination to assess hearing impairment, as shown in Table 1. The subjects carried no other genetic mutations known to cause hearing loss.Table 1 Audiometry Results From Family Members with the A3243G Mutation

The blood samples of these subjects were collected, and the 3243 region of the tRNA^leu gene was amplified via standard PCR. The PCR products were subsequently treated with the restriction enzyme ApaI and visualized on a PAGE gel. The normal undigested PCR product is 161 bp in length, but the PCR product amplified from the mutant A3243G is digested into two fragments by ApaI.

Figure 1 PAGE visualization of PCR products following ApaI digestion
Adapted from Hadjivasiliou Z, Pomiankowski A, Seymour RM, Lane N. Selection for mitonuclear co-adaptation could favour the evolution of two sexes. Proc Biol Sci. 2012;279(1734) :1865-72.
-Which of the following would be true regarding the inheritance of the A3243G mutation? (Note: Assume affected individuals inherited the mutation.)

Quizplus · Accepted Answer

11ecba2d_0f7c_e238_a3bf_6572b7301ceb_MD0008_00 Mitochondria are cellular organelles that have their own genome; their main functions include ATP generation, heat production, and beta-oxidation of fatty acids. Mitochondrial genes are extranuclear and inherited in a distinctly different manner than nuclear genes (autosomal and sex-linked). During fertilization, mitochondria within sperm do not pass into the ovum; therefore, only maternal mitochondria are transmitted to the fetus. Only affected females transmit abnormal mitochondria to offspring; transmission never occurs through males, even if they are affected. As a result, only affected mothers with the mtDNA A3243G mutation can pass it on to their offspring. (Choice A) Only one copy of the dominant allele of the gene is necessary to inherit an X-linked dominant condition. These diseases are characterized by a lack of father-son transmission, but all daughters of an affected father are affected. Affected mothers have a 50% probability of having an affected child. (Choice C) Affected males have asymptomatic carrier mothers in X-linked recessive conditions, which are inherited via the X chromosome. Two mutant alleles must be inherited to cause disease in females (XX), but only one mutant allele is required to cause the disease in males (XY). (Choice D) Autosomal recessive conditions require the presence of two copies of the defective gene for disease manifestation and show no predilection for males or females. About 25% of children are affected if both parents carry one copy of the defective gene (most common scenario). Educational objective: Mitochondria have their own genome, known as mitochondrial DNA, which is inherited in a maternal fashion (ie, no paternal contribution). Mitochondria within sperm are not transferred into the ovum during fertilization; therefore, males never pass on their mitochondria.