Identifying the inflammatory pathways of genes upregulated in LADMAC cells exposed to BCM7

Casein is the main protein present in milk and other dairy products. Beta-casein is one of the 3 major proteins in milk. Beta-casomorphin-9 (BCM9) was the original beta-casein protein found in milk, specifically cow\u27s milk. However, a genetic mutation occurred and the 67th amino acid in the BCM9, proline, mutated to histidine (P67H) creating Beta-casamorphin-7 (BCM7). The protein BCM7 gets cleaved in the small intestine, making it readily absorbed in the body. In previous unpublished studies they found that murine leukocytes (LADMAC cells) showed an increase in inflammation when exposed to BCM7, as compared to BCM9. Therefore, the goal of this experiment is to find the inflammatory pathway of genes upregulated in LADMAC cells when exposed to BCM7. The 5 genes we tested were: PTGES, PTGS1, PTGS2, TNFα and NF-ĸB. Quantitative polymerase chain reaction (qPCR) was used to identify upregulated inflammatory genes in the LADMAC cells exposed to BCM7, BCM9, lipopolysaccharide (LPS, positive control) and phosphate-buffered saline (PBS, negative control). Our results showed that none of the genes were upregulated when exposed to BCM7or BCM9. These genes are also a part of the cyclooxygenase pathway, which implies that an inhibitor of this pathway will not stop inflammation caused by BCM7 or BCM9. Although we did not identify the inflammatory pathway upregulated by BCM7, we were still able to do the opposite. We identified a pathway which is definitely not turned on

Microduplications of 16p11.2 are associated with schizophrenia

Recurrent microdeletions and microduplications of a 600 kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1-3. Here we report the strong association of 16p11.2 microduplications with schizophrenia in two large cohorts. In the primary sample, the microduplication was detected in 12/1906 (0.63%) cases and 1/3971 (0.03%) controls (P=1.2×10-5, OR=25.8). In the replication sample, the microduplication was detected in 9/2645 (0.34%) cases and 1/2420 (0.04%) controls (P=0.022, OR=8.3). For the series combined, microduplication of 16p11.2 was associated with 14.5-fold increased risk of schizophrenia (95% C.I. [3.3, 62]). A meta-analysis of multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. The reciprocal microdeletion was associated only with autism and developmental disorders. Analysis of patient clinical data showed that head circumference was significantly larger in patients with the microdeletion compared with patients with the microduplication (P = 0.0007). Our results suggest that the microduplication of 16p11.2 confers substantial risk for schizophrenia and other psychiatric disorders, whereas the reciprocal microdeletion is associated with contrasting clinical features

Microduplications of 16p11.2 are associated with schizophrenia

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1,2,3. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 × 10−5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 × 10−7), bipolar disorder (P = 0.017) and autism (P = 1.9 × 10−7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 × 10−13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007)

Reduced transcript expression of genes affected by inherited and de novo CNVs in autism

Individuals with autism are more likely to carry rare inherited and de novo copy number variants (CNVs). However, further research is needed to establish which CNVs are causal and the mechanisms by which these CNVs influence autism. We examined genomic DNA of children with autism (N=41) and healthy controls (N=367) for rare CNVs using a high-resolution array comparative genomic hybridization platform. We show that individuals with autism are more likely to harbor rare CNVs as small as ∼10 kb, a threshold not previously detectable, and that CNVs in cases disproportionately affect genes involved in transcription, nervous system development, and receptor activity. We also show that a subset of genes that have known or suspected allele-specific or imprinting effects and are within rare-case CNVs may undergo loss of transcript expression. In particular, expression of CNTNAP2 and ZNF214 are decreased in probands compared with their unaffected transmitting parents. Furthermore, expression of PRODH and ARID1B, two genes affected by de novo CNVs, are decreased in probands compared with controls. These results suggest that for some genes affected by CNVs in autism, reduced transcript expression may be a mechanism of pathogenesis during neurodevelopment

Microduplications of 16p11.2 are associated with schizophrenia.

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders(1-3). We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007)