qPCR assays were also used to detect HMX1-ECR CNVs in 61 patients with other types mictrotia. Dual-luciferase assays were used to detect the enhancer function. Precise breakpoints in F1 and F2 were identified by gap-PCR and sanger sequencing. Quantitative real-time polymerase chain reaction (qPCR) was used to validate and determine the extent of identified CNVs containing HMX1-ECR region. Array comparative genomic hybridization (aCGH) was then performed to detect CNVs in the other four families, F2-F5. Whole genome sequencing was performed to screen all SNVs and CNVs in the candidate disease locus. Single Nucleotide polymorphism (SNP) array was performed to map the disease locus and detect CNVs on a genome scale primarily in the largest family (F1). Here we recruited five Chinese families with isolated bilateral concha-type microtia, and attempt to identify the underlying genetic causes. To date, no genetic defects responsible for isolated human microtia has been reported except for mutations in HOXA2. Copy number variations (CNVs) of a downstream evolutionarily conserved enhancer region (ECR) of Hmx1 associated with ear and eye abnormalities have been reported in different animals, but not yet in human. The H6 family homeobox 1 transcription factor gene (HMX1) plays an important role in craniofacial structures development. Concha-type microtia is considered to be a mild form. Microtia is a congenital anomaly of ear that ranges in severity from mild structural abnormalities to complete absence of the outer ears. In the tunicate Ciona intestinalis, the homeobox transcription factor Hmx drives differentiation of bipolar tail neurons, indicating conserved regulation and function, and homology with cranial sensory ganglia in higher vertebrates. These experiments demonstrate regulatory and functional conservation between Ciona and vertebrate Hmx, and point to bipolar tail neurons as homologues of cranial sensory ganglia. We also show notably robust vertebrate Hmx enhancer function in Ciona, demonstrating that deep conservation of the upstream regulatory network spans the evolutionary origin of vertebrates. Using Ciona and lamprey transgenesis, we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx expression in the stem-vertebrate lineage.
Here we show that the homeobox transcription factor Hmx is a constitutive component of vertebrate sensory ganglion development and that in the tunicate Ciona intestinalis, Hmx is necessary and sufficient to drive the differentiation programme of bipolar tail neurons, cells previously thought to be homologues of neural crest2,3. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia, whose neurons arise predominantly from cranial placodes however, the understanding of the evolutionary origin of placodes and cranial sensory ganglia is hampered by the anatomical differences between living lineages and the difficulty in assigning homology between cell types and structures. What-ever I can do to make them stay with me a little longer I will.The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle1. I have many that last 3-5 years of age with-out any tumors and major health issues. I really feel the worst part of owning rats is that they just do not live long enough, it aches the heart. I have found what works for us here to allow the rats to be raised happy. There are MANY opinions and outdated information out there. I have been breeding for 20+ years and have learned so many things about rats and their care. I will not send more than one a month if at all. You may sign up for the newsletter by joining the website. I do try and send out a newsletter about things to come through the month, litters and what we may be planning. I may not always be available and many emails are often answered late in the evening or on weekends. My rats are raised in my home around our 'normal' day to day, work, play and life. Under "how to adopt" you will find information on adoption and our policies. On the "informational" tab you will find links and articles I enjoy. Please use the navigation bar at the top of this page to view our policies, and who may be available for adoption on the "available" page.
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