Lecture 12: Single Gene Disorders: Autosomal Dominant and Recessive Inheritance

Which term describes the specific version of a gene at a particular location in the genome?

In genetics, what is the definition of 'phenotype'?

What does it mean for an allele to be 'dominant'?

If 'B' represents the dominant allele for brown eyes and 'b' represents the recessive allele for blue eyes, what genotype(s) would result in a person having brown eyes?

What is the purpose of a Punnett square?

In a pedigree, what shape typically represents a male?

What does a shaded symbol in a pedigree usually indicate?

In pedigree analysis, what does a single line connecting a male and a female usually represent?

What is a consanguineous mating on a pedigree?

Which type of mutation results in a change in a single nucleotide that leads to a different amino acid being coded for?

What is the consequence of a nonsense mutation?

What type of mutation involves the insertion or deletion of nucleotides that disrupts the reading frame of a gene?

Which of the following best describes a 'gain of function' mutation?

What characterizes a 'loss of function' mutation?

In autosomal dominant inheritance, if one parent is affected (heterozygous) and the other is unaffected, what is the probability that their child will inherit the disease?

Which of the following is a characteristic of autosomal dominant inheritance patterns?

What is a key characteristic of autosomal recessive inheritance?

In autosomal recessive inheritance, if both parents are carriers, what is the probability that their child will be affected?

Achondroplasia, a form of dwarfism, is caused by a gain-of-function mutation in the FGFR3 gene. What is the effect of this mutation?

Marfan syndrome is caused by a mutation in the fibrillin-1 (FBN1) gene, leading to abnormal TGF-β signaling. What is the normal function of FBN1?

What is the underlying genetic defect in Familial Hypercholesterolemia?

Which of the following is an example of a disease that displays reduced or incomplete penetrance?

What is the function of the CFTR protein, which is mutated in cystic fibrosis?

The most common form of Tay-Sachs disease, infantile Tay-Sachs, is characterized by neurological deterioration beginning at 3-6 months, with a life expectancy of 2-4 years. This is due to the deficiency of which enzyme?

What is meant by the term 'allelic heterogeneity'?

A couple, both asymptomatic for a certain autosomal recessive disorder, have three children. Two are healthy, while one is affected. What is the probability that their next child will also be affected?

Neurofibromatosis type 1 (NF1) displays variable expressivity. What does this suggest about the presentation of NF1 in different individuals?

Li-Fraumeni syndrome is an autosomal dominant cancer syndrome. An individual inherits one mutated allele of a tumor suppressor gene. Why is the chance that the other allele will undergo mutation in that individual very high?

A researcher is studying a novel autosomal recessive disorder. They identify a family where both parents are healthy and have one affected child. If the parents have another child, what is the probability that this child will be a carrier of the disorder but not affected?

A genetic counselor is analyzing a pedigree for a rare disorder. They observe that an unaffected couple has multiple affected children, but neither parent has any family history of the condition. What is the most likely explanation for this inheritance pattern?

In the context of autosomal dominant disorders with age-dependent penetrance, consider a scenario where an individual inheriting the disease-causing allele does not manifest the phenotype until late adulthood. What is the most plausible biological mechanism underlying this phenomenon?

Consider a hypothetical scenario where a novel gene, 'LONGEVITY1,' is discovered to play a crucial role in DNA repair and cellular senescence. Homozygous loss-of-function mutations in 'LONGEVITY1' result in a significantly shortened lifespan and increased susceptibility to various age-related diseases. However, heterozygotes for this mutation exhibit only a subtle reduction in lifespan compared to individuals with two wild-type alleles. If 'LONGEVITY1' is located on an autosome, what is the most likely mode of inheritance for the 'shortened lifespan' phenotype associated with its mutations?

In a scenario involving a novel autosomal recessive metabolic disorder, affected individuals exhibit a deficiency in a crucial enzyme responsible for the detoxification of a specific environmental toxin. Heterozygous carriers of the disease allele display normal enzymatic activity under typical conditions. However, upon exposure to considerably elevated levels of the environmental toxin, carriers exhibit a mild but detectable reduction in enzymatic function. What is the most precise classification of the relationship between genotype and phenotype in these carriers?

A research team discovers a novel gene that strongly influences the severity of asthma. Certain polymorphisms within this gene are found to either exacerbate or ameliorate the effects of known asthma-related genes. These polymorphisms do not directly cause asthma but significantly alter its phenotypic expression. What is the most accurate classification of this newly discovered gene?

Consider a complex signaling pathway involving several proteins, where a dominant mutation in one of the upstream kinases results in constitutive activation of the pathway, leading to uncontrolled cell proliferation. A researcher identifies a compound that specifically inhibits the activity of a downstream transcription factor in this pathway, effectively blocking the proliferative signal. If this compound is administered to individuals carrying the dominant kinase mutation, what is the most likely effect from a genetics perspective?

A geneticist is studying a population where a particular autosomal recessive disorder has a significantly higher prevalence than predicted based on the calculated carrier frequency. Despite the population not being geographically isolated, there's a strong cultural preference for marriage within a specific religious subgroup. Additionally, a subset of this population practices consanguineous marriages at a rate much higher than the global average. What is the most likely explanation for the elevated prevalence of the disorder in this population?

Consider a scenario where a novel drug is being developed to mitigate the symptoms of an autosomal dominant disorder. During clinical trials, it's observed that individuals with a specific genetic background (particular set of alleles at other loci) respond exceptionally well to the drug, experiencing near-complete remission of symptoms. In contrast, individuals lacking this background show only a modest improvement. From a genetics perspective, how could the genetic background be classified?

Consider a scenario where a child is diagnosed with an autosomal dominant disorder, but neither parent exhibits any signs or symptoms of the disease, and comprehensive genetic testing rules out non-paternity. Furthermore, the child's sibling is also unaffected as are all other family members. What is the most likely genetic explanation for this observation?

Two parents, who are both phenotypically normal, have a child diagnosed with an autosomal recessive disorder caused by a mutation in a gene responsible for protein folding in the endoplasmic reticulum. Further investigation reveals that the child is homozygous for the mutation, yet the parents' genotyping shows that while both carry the mutation, they each have a different mutation. How can one best explain this observation?

In a population genetics study, it is observed that a particular autosomal recessive disorder is more prevalent in offspring from first-cousin marriages compared to the general population. However, within the group of first-cousin marriages, there is considerable variation in whether or not offspring are affected. What term best describes this observation from the perspective of quantitative genetics?

A research team is investigating a newly discovered autosomal dominant disorder associated with a gain-of-function mutation in a receptor tyrosine kinase. The mutation leads to constitutive activation of downstream signaling pathways, promoting cellular proliferation and tumor formation. However, the onset and severity of tumor development vary considerably among individuals carrying the same mutation. What is the best explanation for this phenomenon?

A researcher identifies a family with a history of a rare autosomal dominant neurological disorder. Upon analyzing the family's genetic data, the researcher finds that several individuals who carry the disease-causing allele do not exhibit any clinical signs of the disorder, even at advanced ages. Further investigation reveals that these individuals possess a specific variant of a microRNA gene that targets and reduces the expression of the mutated disease gene. How would you best define the phenomenon observed in these asymptomatic carriers?

An autosomal recessive disorder manifests with variable severity; some individuals are severely affected while others have mild symptoms. Research suggests the variation is not due to environmental factors or other mutations within the primary disease gene. Instead, it is hypothesized that the disorder's expression is modulated by variants in genes encoding heat shock proteins (HSPs), crucial for protein folding and stability. What is the best way to characterize the role of HSP genes in this specific observation?

A genetic counselor is advising a couple where both partners are carriers for an autosomal recessive metabolic disorder. Their first child is affected by the disorder. They seek guidance on the recurrence risk for future pregnancies. What is the most precise estimate of the probability that their next child will also be affected by the disorder, considering standard Mendelian inheritance?

A researcher is investigating a family with a history of an autosomal dominant disorder characterized by progressive neurodegeneration. Upon analyzing the inheritance pattern, the researcher observes that the age of onset of the disorder tends to be earlier and the symptoms more severe in subsequent generations. What is the most likely genetic phenomenon underlying this observation?

A genetics researcher is investigating a rare autosomal recessive disorder characterized by a deficiency in a specific enzyme. The researcher identifies a family in which both parents are healthy but have one affected child. Upon sequencing the relevant gene in the affected child, it is discovered that the child is heterozygous for two different loss-of-function mutations. What is the most accurate term for this genetic state?

A researcher is studying a family with a history of a rare autosomal dominant disorder. Upon examining the pedigree, the researcher notices that several individuals who carry the disease-causing allele do not exhibit any signs or symptoms of the disorder. Further investigation reveals that these individuals also possess a specific variant of a gene that encodes a chaperone protein, responsible for assisting in the proper folding of other proteins. What is the most likely explanation for the lack of phenotypic expression in these individuals?

In the context of autosomal recessive inheritance, consanguinity is known to increase the risk of offspring being affected by rare disorders. Consider a scenario where a couple, who are first cousins, are planning to have children. Both are phenotypically normal but are concerned about the possibility of having a child with a specific rare autosomal recessive disorder prevalent in their community. They seek genetic counseling to assess their risk. Which of the following is the primary reason why consanguinity elevates this risk?

A researcher discovers a new mutation in the promoter region of a gene essential for embryonic development. Individuals carrying this mutation exhibit drastically reduced expression of the gene, leading to embryonic lethality. However, in rare instances, some individuals with the mutation survive to adulthood but exhibit a range of developmental abnormalities with varying degrees of severity. What phenomenon most likely accounts for the survival of these individuals?

A geneticist is studying an autosomal dominant disorder characterized by progressive muscle weakness. The geneticist identifies a family in which one parent is affected, but their child, who inherited the disease-causing allele, does not develop any symptoms until late in life, much later than the parent. This phenomenon is observed even through the child is confirmed to have inherited the disease allele. What is the most likely explanation?

A couple, both identified as carriers for two different autosomal recessive disorders (disorder A and disorder B), seeks genetic counseling. The gene for disorder A and the gene for disorder B are located on different chromosomes. What is the probability that their child will inherit at least one copy of each of the mutated genes (i.e., being a carrier for both disorders)?

A researcher is investigating a family with a history of a rare autosomal recessive disorder. The researcher plans to use homozygosity mapping to identify the disease-causing gene. However, the researcher discovers that the affected individuals in the family are homozygous across large portions of their genomes, even regions not linked to the disease. What is the most likely explanation for this observation?

Consider a gene with a known loss-of-function mutation that causes a severe autosomal recessive disorder. Researchers identify a family where the parental genotypes and phenotypes do not align with expected Mendelian inheritance patterns. Specifically, one child presents with the disorder despite only inheriting one copy of the mutated gene from a carrier mother; the father isn't a carrier as confirmed by molecular testing of multiple tissues. What is the most plausible explanation for this discrepancy?

A genetic study reveals that the severity of an autosomal dominant disorder is correlated with the number of CAG repeats in the coding region of the disease-causing gene. Individuals with a higher number of repeats exhibit earlier onset and more severe symptoms. What genetic phenomenon is likely responsible for this correlation?

A study identifies a novel missense mutation in a gene encoding a structural protein. While some individuals carrying this mutation exhibit a severe phenotype, others carrying the same mutation show mild or no symptoms. All individuals show the same level and type of the mutant protein. Further experiments determine that the protein interacts with a variety of other proteins, but only some are present in certain cell types. This interaction also increases the amount of the initial mutated protein. What genetic concept is most likely responsible?

You discover a family with an autosomal dominant intellectual disability, in which members that inherit the causal variant have some degree of intellectual disability. You perform whole genome sequencing on members of this family and perform a genome wide association study (GWAS). What would you expect to find if no SNPS or other variants are found to be statistically significant?

A researcher is studying a family affected by an autosomal dominant disorder with complete penetrance. However, after extensive analysis of the pedigree, they identify one individual who inherited the disease-causing allele but does not show any symptoms of the disorder. This individual is confirmed to carry the mutated allele through genetic testing and has lived well past the typical age of onset. What genetic phenomenon could explain this observation?