Limb development genes underlie variation in human fingerprint patterns

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized “pattern-block” correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning

Improved phylogenetic resolution for Y-chromosome Haplogroup O2a1c-002611

Y-chromosome Haplogroup O2a1c-002611 is one of the dominant lineages of East Asians and Southeast Asians. However, its internal phylogeny remains insufficiently investigated. In this study, we genotyped 89 new highly informative single nucleotide polymorphisms (SNPs) in 305 individuals with Haplogroup O2a1c-002611 identified from 2139 Han Chinese males. Two major branches were identified, O2a1c1-F18 and O2a1c2-L133.2 and the first was further divided into two main subclades, O2a1c1a-F11 and O2a1c1b-F449, accounting for 11.13% and 2.20% of Han Chinese, respectively. In Haplogroup O2a1c1a-F11, we also determined seven sublineages with quite different frequency distributions in Han Chinese ranging from 0.187% to 3.553%, implying they might have different demographic history. The reconstructed haplogroup tree for all the major clades within Haplogroup O2a1c-002611 permits better resolution of male lineages in population studies of East Asia and Southeast Asia. The dataset generated in the present study are also valuable for forensic identification and paternity tests in China

Expression of CTTN in ESCC and normal esophageal tissues.

<p>Note:*<i>P</i><0.005.</p

Genome-Wide Gene Expression Profile Analyses Identify CTTN as a Potential Prognostic Marker in Esophageal Cancer

<div><p>Aim</p><p>Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets.</p><p>Methods</p><p>We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR), tissue microarrays (TMAs) and immunohistochemistry (IHC) staining.</p><p>Results</p><p>Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤−1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26) and two underexpressed (HMGCS2 and SORBS2) were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN) was observed in 126/198 (63.6%) of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000), pathologic stage (P = 0.000) and poor survival (P<0.001) of ESCC patients. Furthermore, a significant correlation between CTTN overexpression and shorter disease-specific survival rate was found in different subgroups of ESCC patient stratified by the pathologic stage (P<0.05).</p><p>Conclusion</p><p>Our data provide valuable information for establishing molecules as candidates for prognostic and/or as therapeutic targets.</p></div

Kaplan-Meier plots for the Disease-specific survival rate of ESCC patients.

<p>(A) Kaplan-Meier plots for the Disease-specific survival (DSS) rate of ESCC patients with (n = 126, green line) or without (n = 72, blue line) CTNN overexpression. (B) Kaplan-Meier plots for the DSS rate of ESCC patients with pathologic stage I+IIA (n = 113, blue line) or IIB+III (n = 85, green line).</p

Association between CTTN over-expression and clinicopathologic characteristics of patients with ESCC (n = 198).

<p>*<i>P</i><0.05.</p

Kaplan-Meier plots for the DSS rate in ESCC patients subgrouped into pathologic stage I-IIA (A) and pathologic stage IIB-III (B) as differentiated by with (+) or without (−)-CTTN overexpression.

<p>Kaplan-Meier plots for the DSS rate in ESCC patients subgrouped into pathologic stage I-IIA (A) and pathologic stage IIB-III (B) as differentiated by with (+) or without (−)-CTTN overexpression.</p