Summary:Knowledge of fetal HLA type can be important if cord blood (CB) is being considered as a stem cell source for transplantation. The feasibility of determining the paternally inherited HLA haplotype of a fetus was explored through analysis of fetal DNA in the maternal circulation. A 5-year-old child with relapsed acute leukemia was a candidate for transplantation. The HLA type of the fetal sibling was needed to assist with evaluation of this potential cord blood donor. DNA was isolated from maternal plasma and whole blood. Kinetic PCR using sequence-specific primers for paternal HLA-A, -B, and -DRB1 alleles was performed. Alleles corresponding to one paternal haplotype were detectable in plasma, but not in whole blood. Alleles from the alternative haplotype were not detectable. This demonstrated that the fetus shared at least one haplotype with the patient and therefore arrangements were made to bank the CB. The maternal haplotype of the fetus could not be determined in the presence of maternal DNA. invasively using both cell-associated and cell-free fetal DNA which enters the mother's circulation during pregnancy. Analysis of fetal DNA in maternal plasma has allowed noninvasive prenatal determination of fetal Rh D genotype, 3 and is promising in other conditions. 4 We describe the first noninvasive determination of a paternally inherited fetal HLA haplotype and the use of kinetic PCR to detect fetal DNA in maternal plasma during late third trimester. Non-invasive prenatal HLA typing will be useful for evaluation of CB for transplantation of a family member or banking. Materials, patients and methods Case reportA 5-year-old female with acute leukemia had initial therapy in Mexico. The family relocated to the United States and presented for care at the time of leukemic relapse. Chemotherapy induced a second remission, but the high likelihood of relapse made immediate allogeneic transplantation the preferred treatment. If the fetus were known to be HLAmismatched, transplant from an alternative donor could be pursued immediately. The mother was 36 weeks pregnant with a full sibling to the patient. Family HLA typingHLA typing HLA-A, -B, -C and -DRB1 alleles of the patient, mother and father were determined by automated sequencing of selectively amplified HLA loci or alleles (Figure 1). After birth, HLA-A, -B, and DRB1 types of CB were similarly determined by automated sequencing. Prenatal HLA typing of maternal blood by kinetic PCR

Background: Depression and coronary heart disease (CHD) have common risk mechanisms. Common single nucleotide polymorphisms (SNPs) may be associated with the risk of depression combined with coronary heart disease. Methods: This protocol was designed according to the PRISMA-P guidelines. CENTRAL in the Cochrane Library, MEDLINE Ovid, Embase Ovid, Web of Science, CNKI, CQVIP, SinoMed, Wanfang Data, and ChiCTR will be systematically searched. We will include case-control studies and cohort studies investigating the relationship between gene SNPs and depression and coronary heart disease comorbidities. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias. When measuring dichotomous outcomes, we will use the risk ratio (RR) and 95% confidence interval (95%CIs) in a cohort study and use the odds ratio (OR) and 95% confidence interval (95%CIs) in a case-control study. Five genetic models (allele model, homozygous model, heterozygous model, dominant model, and recessive model) will be evaluated for each included study. Subgroup analysis by ethnicity will be performed. If necessary, post hoc analysis will be made according to different types.Discussion: The purpose of this meta-analysis is to comprehensively study the current evidence and assess the association between single nucleotide polymorphisms and susceptibility of depression in combination with coronary heart disease.Systematic review registration: This protocol was prospectively registered in the PROSPERO (registration number CRD42021229371).