Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

[Q]: Context: Obstetric cholestasis is a cholestatic disease usually commencing in the third trimester of pregnancy and characterized by pruritus, elevation of liver enzymes, and increase in bile acids. The objective of this study was to compare the first trimester serum indicators of obstetric cholestasis with normal pregnancies.', 'Thirty-five patients diagnosed with obstetric cholestasis in a three-year period with first trimester biochemical assessment available were included in the study. Seventy patients with concordant pregnancy weeks, matched-age normal pregnancies were included as the control group. Pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) levels were analyzed.', 'No difference was observed between the two groups in terms of age and week of pregnancy. While the mean PAPP-A level was 0.76 0.31 multiples of the medians (MoM) in the obstetric cholestasis group, it was determined to be 1.5 0.84 in the control group (p = 0.0001). Among the two groups, the hCG levels were found to be higher in the obstetric cholestasis group (1.2 0.79 MoM vs. 0.98 0.53, p = 0.041).
Answer: In this study, the first trimester PAPP-A levels in the obstetric cholestasis cases were found to be significantly lower than the control group. Low PAPP-A levels should be a warning for obstetric cholestasis.
[A]: Are pregnancy-associated plasma protein a levels decreased in obstetric cholestasis?

[Q]: Context: To establish a novel approach for quick and high throughput verification of human gene imprinting.', "By use of a pair of dye-labeled probes, 5' nuclease assay was combined with reverse transcriptase-PCR(RT-PCR) to genotype a coding single nucleotide polymorphism (cSNP), rs705(C/T) of a known imprinted gene, small nuclear ribonucleotide protein N (SNRPN), on both genomic DNA and cDNA of human lymphoblast cell lines.", 'Allele discrimination showed a clear monoallelic expression pattern of SNRPN, which was confirmed by RT-PCR based restriction fragment length polymorphisms. Pedigree analysis verified the paternal origin of expressed allele, which is in consistency with previous report.
Answer: Coding SNP is an ideal marker for detecting gene imprinting by 5' nuclease assay. This approach has also a potentiality to discover differential allele expression of non-imprinted genes in order to find gene cis-acting functional polymorphism.
[A]: Is [ Coding single nucleotide polymorphism an ideal marker for detecting gene imprinting by 5 ' nuclease assay ]?

[Q]: Context: Central core disease is a congenital myopathy, characterized by presence of central core-like areas in muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel. Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. Recent next-generation sequencing methods are now identifying multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.", "In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1 gene identified two different missense mutations: c.14256 A >C polymorphism in exon 98 and c.14693 T >C in exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed because patient's daughter, mother and sister carried only the exon 98's mutation, a synonymous variant that was subsequently found in the frequency of 013-0,05 of alleles. Further next generation sequencing study of the whole RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and 8 polymorphisms in heterozygosis.
Answer: Considering that patient's relatives showed no pathologic phenotype, and the phenotype presented by the patient is within the range observed in other central core disease patients with the same mutation, it was concluded that the c.14256 A >C polymorphism alone is not responsible for disease, and the associated additional silent polymorphisms are not acting as modifiers of the primary pathogenic mutation in the affected patient. The case described above illustrates the present reality where new methods for wide genome screening are becoming more accessible and able to identify a great variety of mutations and polymorphisms of unknown function in patients and their families.
[A]:
Do silent polymorphisms in the RYR1 gene modify the phenotype of the p.4898 I > T pathogenic mutation in central core disease : a case report?