輸血醫學 by 林媽利

The Peopling of East Asia: Putting Together Archaeology, Linguistics and Genetics by Marie Lin, et al.

"台灣血液之母"

Excerpt from 林媽利學術與人生一樣精采 by 陳惠惠

對有些民眾來說，林媽利這三個字聽起來也許有些陌生，但許多急待輸血的人能挽回一命，或許都要靠她長年來的研究結果。

一頭栽進血液研究領域，跟林媽利大學期間得到「再生不良性貧血」，常需輸血脫不了關係。早在一九九八年，林媽利就提出Rh陰性血可以輸陽性血的「陰陽互通」觀念；去年更發明了「玻片凝聚胺法」，只要五分鐘就能分辨能否輸血，不再需要花時間區別血型。

幫台灣原住民找親戚，更是林媽利多年來的研究重心。根據她的研究，台灣閩南、客家人屬於大陸東南沿岸「越族」，而非所謂的「炎黃子孫」，為此，一度被大陸學者點名圍剿。

林媽利不但是獲得聯合國教科文組織推薦，成為台灣第一位入圍「Helena Rubinstein獎」的女性科學家，「世界名人錄」、「科學及工程世界名人錄」、「醫學及生物世界名人錄」上都有她的名字。

接觸過林媽利的人，很難忘記她嬌小的身影，以及學生般清湯掛麵的髮型，講起來話，永遠是不疾不徐、帶著笑意，隱約中透露著堅毅，難以想像她就是馳名國際的輸血醫學專家，而她的人生經驗，比起學術成就，也不遑多讓。

卅幾歲的林媽利，曾因為工作過於勞累，染上肺結核，四十多歲的她，意外發現自己罹患了乳癌。然而，醫界熟知的，除了她的成就，還包括她與心臟外科權威朱樹勳的一段婚姻，這段婚姻在她五十多歲時收場。離婚後，她改嫁相識近四十年、一生守候她的學者郭惠二，譜出國內醫界另一段動人的故事。

* Genetic Determinism by Chang Chiung-fang

* 基因研究已確認台灣人與中國人不同種 by Corinne W.

* SARS帶給閩、客族群的沖激──原來您不是『中原漢人』by

客家小棧

* 永恆的西拉雅族－遺傳基因的研究 by 林媽利, et al.

我們流著不同的血液: 以血型、基因的科學證據揭開台灣各族群身世之謎
by 林媽利

* 林媽利教授談：從組織抗原推論閩南人及客家人─所謂「台灣人」的來源 by 林媽利

Excerpt: 其實我做這麼多研究，很多資源都是從外國來，在台灣像我去申請國家衛生研究院，有時申請不到，有一餐沒一餐的。我的研究一直得到許多國外研究機構的援助，很多外國友人幫我，把試劑寄給我。在荷蘭阿姆斯特丹紅十字會血液中心的 Engelfriet，你知道荷蘭人口比我們少，但荷蘭紅十字會血液中心有五百個人！五百個人在做研究，裡面博士和醫生有七十幾個，他是那裡過去的主任，他也幫我們很多忙。我常常會把這個拿出來講︰馬偕醫院以一個私人財團法人的私立醫院，要做整個好像國家的研究，實在是很……我覺得國家沒有支持的話是很不應該的。還有大陸，雖然他們做得那麼差，但是他們有幾個中心，我在 1988 年到成都血液中心時，那兒就有一百二十幾個研究員。現在他們在北京也成立一個，天津本來也有一個，最近在上海又成立一個研究中心，我們台灣就什麼都沒有啦！我在想好像就只有我們……雖然現在有些醫院在做一些研究，但規模都不大，沒有得到國家的支持，而且我覺得一路走來，沒有多少掌聲……

* 從組織抗原推論閩南人及客家人，所謂「台灣人」的來源 by 林媽利

摘要: 台灣的閩南人及客家人也就是所謂的「台灣人」(以下均以括弧的「台灣人」代表閩南人及客家人)，是近幾世紀以來自中國大陸東南沿海地區移民的後代，在基因上經族群系統發生樹 (phylogenetic tree )及族群相關分析(correspondence analysis)　研究計算後，發現閩南人及客家人是屬於南亞洲人種，這剛好配合民族史的記載，認為「台灣人」是大陸東南沿海原住民「越族」的後代。A33-B58-DRB1*03 (即A33-Cw10-B58-DRB1*03-DQB1*02)是「台灣人」最常見的組織抗原(HLA)半套體，頻率為6.3%，而這半套體在新加坡華人及泰國華人也算是最常見，顯示這是被完整保留下來的古代越族的基因。

討論: 因為HLA是多變異及多樣化的基因系統，所以是研究族群關係很好的材料，HLA在不同族群間所顯示的差異比別的基因系統還要明顯，且利用HLA的半套體研究時差異更顯著，所以是一個很好的研究族群關係的指標。許多半套體由特定的HLA基因構成而經過幾千年許多世代的傳嫡而不改變，而且每個特定的半套體的分佈有其地域的限制。所以HLA半套體在探討相近族群間的關係時是強而有力的基因標誌 (參考資料8)。利用家族的分析是研究多個基因位上HLA半套體的分佈情形最好的方法，雖然過去有幾個有關台灣HLA半套體分佈的研究，都是經統計計算得到的，我們的報告是第一個用家族的分析得到「台灣人」HLA半套體分佈的情形而加以研究的。 A33-B58-DRB1*03是「台灣人」最常見A-B-DR 3個基因位的半套體(6.3%)，且完整的經過千年被保存下來，其相對的五個基因位半套體是同頻率的A33-Cw10-B58-DRB1*03-DQB1*02　(6.3%)。慈濟台灣骨髓登錄也和我們有相似的結果(參考文獻7)，他們經計算也發現A33-B58-DR17(　即DRB1*03　)半套體是「台灣人」最常見的半套體，佔閩南人7137人中5.5%，及客家人714人中5.10%。A33-B58-DRB1*03半套體也在東南亞(泰國華人7.1%，新加坡華人4.4%，參考文獻5)及北方亞洲人發現(在烏魯木齊的漢人3.5%，蒙古的Khalha族3.4%、烏魯木齊的Uygur 1.8%、哥薩克人 1.8%、韓國人1.2%，參考文獻9、10)，而同樣的5個基因位的半套體在泰人可以看到(泰國人2.2%，Black Thai 2.8% ，參考文獻11)。另一有趣的所見是HLA-A,B 2個基因位的半套體A33-B58在南方漢人(檢驗人數為138人，取自湖南及福建2省，參考文獻5)只有2.4%，如再加上檢測DR基因位而成A-B-DR半套體時，因所得數目太小在11th IHW變成無意義的數目。另一方面較早期的報告A33-B17( B58是屬於B17 )的半套體在南方漢人的頻率(檢驗844人)是1.53%而南方少數民族(檢驗621人)的頻率為1.29%(參考文獻12)。在另一個報告，A33-Cw10-B58在北方漢人發現(檢驗196人)為3.1% (參考文獻13)，但這跟隨的DR基因在東北亞洲人應該是DR13而不是在「台灣人」的DR3，所以B58-DR3半套體的分佈是明顯的集中在東南亞的族群(參考文獻8)。A33-Cw10-B58-DRB1*03-DQB1*02的3或5個基因位的半套體雖然可在東亞或東南亞看到，但最高的頻率是在「台灣人」、新加坡華人及泰國華人，而這三個族群的祖先都是在近幾百年才從大陸東南沿海移民出去的，因此這半套體可以說是這三個族群一直保存下來的遺傳標誌。

「台灣人」第二個常見的3個基因位的半套體在我們的研究是A2-B46-DRB1*09 (3.0%)，根據文獻也在別的族群發現，包括新加坡華人(7.7%)、越南人(5.2%)、南方漢人(5.1%)、泰國人(4.7%)及泰國華人(2.4%)，而相對的5個基因位的半套體A2-Cw1-B46-DRB1*09-DQB1*0303 (2.7%)也在Black Thai (8.3%)，Dai　Lui(泰北的傣族5.1%) 及泰國人(2.1%) 看到，顯示為亞洲南方族群的半套體(參考文獻5、8、11)。就單單從許多HLA研究的結果，長久以來即已經知道北方漢人及南方漢人在基因上不同(參考文獻7、8、14、15)，這和發現的中國史前資料及有文字記載以後的歷史相配合。「中原文化」是在中國北方黃河的黃土高原發展出來的，從最近挖掘出來的粟米(millets)可以追朔到公元前6到7千年之久。中原文化在夏、商、周時期是在長江以北，直到秦朝(公元前221-206年)後政治的勢力才及於中國大陸的中南方(參考文獻17)。最近的考古研究發現在中國大陸南方，在同一個時候存在另一個獨立且不同於中原文化的「越沿海文化」，從長江三角洲到越南北方的紅河三角洲(參考文獻18)。但是南方的歷史只從公元前500年左右吳越相爭之前才開始有的，越王勾踐的「臥薪嚐膽」復國的故事是大家所熟悉的。「越族」是指大陸東南沿海( 浙江、福建、廣東及廣西 )的居民，在漢朝以前因為這地區文化的多樣性而被稱為「百越」。除了春秋戰國的吳越相爭及在漢朝時期部份越族的北移外，在中國的歷史(即中原文化的歷史)並沒有太多有關越族的記載，因為在中國的歷史除了中原文化外，其他族群均屬「蠻族」(參考文獻17、19)。閩人及台灣閩南人的祖先是居住在福建的越族，根據林惠祥(參考文獻17)及Meacham的研究(參考文獻19)，今日的閩人是東南沿海地區原住民「越族」的後代，雖然在秦漢及接下來的魏晉南北朝五胡亂華時期，因為戰亂北方中原人士紛紛南遷，而可能引起部份有限的中原基因的滲入。當「越」的文化漸漸被「漢」化後，「越族」就在歷史上被改名成「漢族」，導至今日台灣的閩南人錯誤的判斷且自認為是純種北方漢族的後代。在中國歷史上許多民族接受漢文化而漢化，後來這些人民也常常宣稱他們是漢族，這是因為在過去漢文化是強勢文化，所以當了漢人可得到利益及社會地位(參考文獻17、19、20)。在客家人的情形也是相似，在南宋(1127-1279AD)或更早的時期有少數的中原家族南遷到東南沿海的山區，這些人以強勢的漢文化在文化及語言上影響周遭的原住民，特別是住在廣東的越族，所以以早期的少數中原移民加上眾多的越族而成客家族群(參考文獻21)。

我們以統計得到基因距離D及DA建構的族群系統發生樹，顯示閩南人與客家人有相當一致的基因，所以先合在一起，然後再和泰國華人、新加坡華人合併成一枝，而這些族群都是起緣於東南沿岸的原住民「越族」，其中最重要的是「台灣人」明顯的和北方漢人分開。慈濟骨髓登錄的資料建構的族群系統發生樹顯示「台灣人」和南方漢人合併，但和北方漢人分開(參考文獻8)。其他許多HLA的研究，及別的基因和遺傳標誌，像免疫球蛋白(參考文獻22)、血型(參考文獻23)、葡萄糖六磷酸去氫酵素(參考文獻24)及染色體DNA微衛星(參考文獻25)等，都明顯的把「台灣人」和北方漢人分開。不久前中國北京的中科院遺傳研究所和美國史坦福大學Cavalli-Sforza合作研究，以中國人的姓氏及三種簡單的血型分佈情形將北方漢人與南方漢人分開(參考文獻20)，在該項研究中南方漢人再被分為3群，即長江下游以上海為中心的一群、長江流域的一群及另一群屬於越族的東南沿海地區及島嶼(包括台灣)的居民。中國人的姓氏約有4000年的歷史而且是由男性傳承，所以可以認為代表Y染色體的遺傳，該研究更借著中國的28省加上台灣以ABO、MN及Rh(D) 血型的基因頻率而計算出族群的關係，畫製成的第一度及第二度空間上的族群主要相關圖明顯的把東南沿海地區及台灣的居民(即越族)與其他地區的居民分開。

以上資料顯示南方漢人是緣自南方而有別於北方漢人，「台灣人」是古代越族的後代而保存著古代越族的基因A33-Cw10-B58-DRB1*03-DQB1*02。有關「台灣人」與南方漢人的基因距離的遠近，有待將來的研究，因為現在這研究中所用的南方漢人資料有一半是自福建(參考文獻5)。

越族

百越又稱為百越族、越族，泛指古代居於中國南方的族群（人類社會）。

因為有許多支系，所以也就稱百越。其中句吳、于越、東甌、南越等幾支百越中的大族，先後與中原的華夏族融合，成為漢族形成的來源之一，其餘百越中靠近西部和西南部的幾個支系西甌、駒越、駱越等演變為現代中國南方的壯侗語民族以及越南 (Vietnam)、寮國 (Laos)、泰國 (Thailand)、緬甸 (Burma)、印度 (India) 境內的京、佬、泰、撣族、阿洪姆等民族。

起源: 根據有關文獻的記載，早在商、周時期，就有被稱之為「越」的古民族（古代中國人泛稱東南方蠻族為「越」，北方蠻族為「胡」），生活在現今中國的東南及南部地區（王東 2003，3）。春秋晚期至戰國前期，越族曾在今江浙一帶建立強大的越國，共傳8代，歷160多年，與當時中原國家會盟，雄視江淮地區，號稱「霸主」（請參見「勾踐」條目；陳國強 2000）。有學者根據《史記》「越王勾踐世家」的描述，認為越族是夏禹的後代。不過，研究百越族的中國學者宋蜀華認為：「勾踐的祖父夫鐔以上至夏少康庶子無餘，世系不清楚；夏少康經商至周敬王共60餘代，兩者世系相差近1000年，把越王勾踐說成是夏少康的後裔，實難信服」（引自龔佩華 nd）。此外，宋蜀華也認為夏文化和越文化截然不同，因為：「夏人活動地區從未發現過『印紋陶文化』，而『印紋陶』流行地區也從未發現過『二里頭文化』」（引自龔佩華 nd）。

根據目前考古學的證據，距今7000年的浙江「河姆渡文化」遺址，很可能就是古越族所創造出來的文化。河姆渡遺址發現了稻穀、稻草和稻殼的堆積，是當時世界發現最早的稻作文化，後來在黃河流域的裴李崗遺址、賈湖遺址和長江中游流域的彭頭山遺址等地發現了更早的稻作文化。此外，現在的考古學家也普遍認爲，廣泛分佈於中國南方各地的以幾何印紋陶爲主要特徵的文化遺存，可能也是由古越族所創造出來的。最近數十年來的考古發掘表明：這種以幾何印紋陶爲主要特徵的文化遺存，在時間上從4000多年前的新石器時代晚期開始，一直延續到商周秦漢時期，在空間上則遍佈於中國東南地區及嶺南一帶（王東 2003，3）。

歷史: 和「古越族」相關的最早文字記錄涉及「於越」，于越是春秋時期之越國的前身，最晚在商朝的時候就已經存在，雖然沒有參加武王伐紂，但至少曾經北上當周成王的賓客。該國傳至勾踐 (500 B.C.)的時候，他試著向北擴張，曾經沿著江蘇的海岸北上膠州灣。古越族和漢族早期的關係主要在貿易，越人以象牙、玳瑁、翠毛、犀角、玉桂和香木等交換北方的絲帛和手工產品(鍾倫納 2004)。

有觀點認為古籍中的『百越』由『古越族』經過漫長的歷史演變而成。戰國時代文獻中便出現了「百越」這一個新的稱謂。戰國後期，除了有百越這個名稱以外，還有「揚越」這個名稱指代揚州地區的越族。揚州包括今淮南、長江下游和嶺南的東部地區，有時又包括整個嶺南地區。所以揚越實際也是戰國以來至秦漢對越人的另一種泛稱(王東 2003，3；陳國強 2000)。

秦漢時，相關史籍則泛稱中國南方的民族為「越族」，史稱「北方胡、南方越」。由於歷史的發展和變化，至遲在漢朝初期，百越族已經逐漸形成幾個較強盛而明顯的部分，即「東甌」(東海)、「閩越」、「南越」、「西甌」、以及「雒越」(駱越)。東甌在現今浙江省南部的溫州一帶；閩越在今福建省福州一帶；南越在今廣東省境，後來又發展到廣西以及以南地區；西甌則大概分佈在今廣東西部、廣西南部及以南地區；駱(雒)越主要分佈在現今的越南北部與海南島。雲南有滇越,緬北有越裳,這些部分都形成了當時該地的政治中心，比如說閩越第一代君主無諸、東海第一代君主騶搖、以及南越王趙佗，都曾經叱吒風雲過一段不算短的時間(陳國強 2000)。

越族所建立的這些政治中心，後來都被漢武帝征服，改為漢朝的郡縣。此後，百越這個名稱就不見於史載，越族之名也十分罕見(陳國強 2000)。

關於越的名稱: 古代「粵」、「越」通用。越族就是生活在長江以南的一個古老的民族。夏朝稱「于越」；商朝稱「蠻越」或「南越」；周朝稱「揚越」、「荊越」；戰國稱「百越」。宋朝人羅泌的《路史》說：「越常、駱越，甌越、甌皚，且甌、西甌，供人，目深、摧夫、禽人、蒼吾，雜處於現今中國南方各地。在中國歷史上，整個廣大的江南之地，即所謂「交趾至會稽七八千里」，在秦漢以前都是、越區、桂國、損子、產里、海癸、九菌、稽余、北帶、仆句、區吳，是謂百越。」（摘自黃現璠撰《試論百越和百濮的異同》一文）。

文獻上也稱之為百粵、粵，其分佈甚廣，內部「各有種姓」百越族的居住地，他們所使用的古越語（非粵語），與中國北方所使用的古漢語也相差極大，彼此不能通話，古越語是南島語族的始祖。

文化特點: 百越族有自己的民族語言和生活、文化特點。百越語為黏著型，不同於漢語的單音成義，故百越語譯成漢語時一字常譯為兩字，如愛為「憐職」，熱為「煦蝦」。有人認為越語與今壯侗語系的語言十分接近。

百越族的生活、風俗習慣也有特點，主要是：水稻種植,椎髻,著貫頭衣,鑿齒; 斷髮紋身,雞卜；契臂為盟；多食蛇蛤海產；巢居,干欄式建築；善使舟及水戰；以及善鑄銅器，如青銅劍、銅鐸(大鈴)(與彌生時代文化相似),銅鼓,獵頭,食人,喜吃檳榔,男女混浴,喜鬥雞等。

文化影響: 雖然在今天已經找不到一個名字叫做「百越族」的民族或族群，不過，百越文化事實上卻透過種種不同的方式，在很多不同民族的文化裡面留下了種種痕跡。以下是一些比較值得加以探討的議題。

在新石器時代，該古代民族文化遺存中有一種以幾何印紋陶為特徵，該族是一個崇拜龍的圖騰的部族，有紋身的習俗，生活於水鄉，自比是龍的子孫。有咀嚼檳榔黑齒的習慣。

對於當今某些民族語言的影響: 現有的一些語言學研究均指出，在百越族被漢化以後，其所使用的很多字詞，卻依舊遺留在不少民族現在的語彙當中，比如說屬於侗壯語系和苗瑤語系的中國某些少數民族，被歸為漢語方言的一些南方方言，甚至包括印尼、馬來西亞、夏威夷、紐西蘭等地的南島民族，其語言中都可以找到屬於古越語的「同源字」(盧溢棋 1997)。比如說古越語的「蜘蛛」(***lakwa)一詞，就可以在鶴佬語(發音為lâ-giâ)、客家話(發音為lakia)、畲語(發音為laukhoe)、馬來/印尼語(發音為lawa、lawa-lawa、labah-labah)、夏威夷語(發音為lanalana、nananana)以及紐西蘭毛利人的拉巴怒伊語(Rapanui)(發音為nanai)等語言當中找到類似的發音(Hoklo.org nd)。日本語的字眼很多來自南島語族。

對於當今某些民族之習俗的影響: 端午節習俗是他們創立用於祭祖的習俗，在歷史發展中已經融合到漢族中去了

所謂的「拾骨葬」，或稱「二次葬」，在中國長江以南各地，比如說江蘇、浙江、福建、廣東、台灣的漢人，以及很多少數民族，比如說壯族、藏族，都有這種習俗。事實上，一直到現在，台灣、香港採用這種喪葬儀式十分普遍，中國大陸已實施火葬。拾骨葬是土葬數年後開棺取骨，然後將全副骨骼一一置入一稱為「金斗」的陶甕當中。直到馬達加斯加也有此習俗。

這種拾骨葬的習俗，事實上並不是漢族所固有的，而是環太平洋原始民族中普遍分佈的一種文化特質，廣及中國大陸、東南和東北亞洲、南太平洋諸島、以及南北美洲。根據台灣中央研究院民族學學者凌純聲的研究，整個洗骨文化圈裏諸民族所採行的洗骨文化，基本上均為來自相同起源的一個文化習俗，而這個習俗最早的起源地，正是百越族所分佈的華南地區。倭人的水稻種植，斷髮紋身，與生活習慣與百越人出奇相似。

* The Origin of Minnan & Hakka, the So-Called "Taiwanese" Inferred by HLA Study by Marie Lin

Abstract: The Minnan and Hakka people groups, the so-called "Taiwanese", are the descendants of early settlers from the southeast coast of China during the last few centuries. Genetically they showed affinities to southern Asian populations, as determined by phylogenetic trees and correspondence analysis calculated from HLA allele frequencies. This corresponds historically with the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of "pure" northern Han Chinese. A33-B58-DRB1*03 (A33-Cw10-B58-DRB1*03-DQB1*02), the most common HLA haplotype among "Taiwanese", with a haplotype frequency of 6.3%, has also been found to be the most common haplotype among Thai-Chinese and Singapore Chinese, two other populations also originating from the southeast coast of China. These observations suggests that this haplotype is the most well-conserved ancient haplotype of the Yueh.

Discussion: Because of the high degree of the polymorphism of HLA system, it is a useful genetic marker for the characterization of human populations and analysis of their relationships for anthropological purposes. Differences in the distribution of HLA alleles among various human populations are more marked when compared to other genetic markers. This becomes even more obvious if HLA haplotypes (particular combinations of alleles) are used as an index. It is interesting that many haplotypes were found to have a unique organization of HLA genes that have been well-conserved through thousands of years and also each characteristic haplotype shows a limited regional distribution. Therefore the HLA haplotype is a powerful marker and is useful for surveys among closely related ethnic groups (8). Family studies have been found to be the best method for studying multilocus HLA haplotype distribution in Taiwan, this studies is the first report based on family study in “Taiwanese” (Minnan and Hakka).

A33-B58-DRB1*03 was found to be the most common and also the best conserved A-B-DR three-locus haplotype among “Taiwanese” (6.3%), was exclusively related to the most common five locus haplotype, A33-Cw10-B58-DRB1*03-DQB1*02 (6.3%). Similar to our results, the haplotype A33-B58-DR17 (DRB1*03) was also proven to be the most common haplotype in Taiwan among Minnan (n = 7137, 5.59%) and Hakka (n = 714, 5.10%) by the Tzu Chi Taiwan Marrow Donor Registry as estimated by the maximum likelihood method (7). The three-locus haplotype A33-B58-DRB1*03 has also been found among southeast Asians (Thai-Chinese 7.1%; Singapore Chinese 4.4%) (5) and northern Asians (Han in Urumchi, China 3.5%; Khalha in Mongolia 3.4%; Uygur in Urumchi, China 1.8%; Kazakhs in Urumchi, China 1.8%; Korean 1.2%) (9, 10). The five-locus haplotype has also been found in Thais (Present-day Thais 2.2%; Black Thai 2.8%) (11). It is interesting to note that the HLA-A, B two-locus haplotype A33-B58 among southern Han (n = 138, samples collected in Human and Fuchien) was reported to be only 2.4%, with no significant A-B-DR three-locus haplotype frequency at the 11 IHW (5), while in an earlier report the A33-B17 haplotype frequency among southern Han (n = 844) was 1.53%, and for southern minorities (n = 621) was 1.29% (12). In another report, the haplotype A33-Cw10-B58 was found among northern Han (n = 196, 3.1%), however, the most frequently associated DR gene with this haplotype in northeast Asians is more likely DR13 than DR3 (13), and the distribution of haplotype B58-DR3 was found clearly focused in southeast Asian population (8). Therefore, although three- to five-locus haplotype of A33-Cw10-B58-DRB1*03-DQB1*02 has been found to be distributed among all east and southeast Asians, however, the highest frequencies have been found in “Taiwanese”, Singapore Chinese and Thai-Chinese, and these three populations are presumed to be the descendants on early settlers from the southeast coast of China. Therefore, this haplotype is probably the most well-conserved haplotype among these three populations.

The second most common three locus haplotype among “Taiwanese” in this study A2-B46-DRB1*09 (3.0%) has also been found in Singapore Chinese (7.7%); Vietnamese (5.2%); southern Han (5.1%); Thais (4.7%) and Thai-Chinese (2.4%) (5). The corresponding five-locus haplotype A2-Cw1-B46-DRB1*09-DQB1*0303 (2.7%) has also been found in Black Thai (8.3%), Dai Lui (Thais, 5.1%), and present-day Thais (2.1%) (11). This haplotype is thus characteristic for southern Asians (8).

It is well known from the results of HLA studies that there are genetic differences between southern and northern Han Chinese (7, 8, 14, 15). This corresponds well with the prehistory and history of China. The Central Plains (Chung Yuan) culture developed in the loess region of the Hunag Ho (Yellow River) basin in the north of China. And was dated to sixth or even seventh millennium BC from excavated millets (16). This culture went through the Shia civilization, followed by the Shang and Chou Dynasties and was limited to the north (north of Yangtze River). Only in the Chin Dynasty (221 – 206 B.C.), there was political control over the central region of the south gained (17). Recent new archeological discoveries showed that in the south of China there was an independent Yueh coastal culture (from the Yangtze delta to the Hong river delta in North Vietnam) in existence almost at the same period of time (18). However, the history of the south only began around 500 B.C. just before the battles between two countries of Yueh and Wu (17). There is a well known story about the King of the Yueh who slept on firewood for mattress and had gall hung over his bed to remind him of the bitterness of his defeat by Wu which finally enabled him to win the battle, and resulted in national recovery. The Yueh people lived along southeast coast of China (Chechiang, Fuchien, Kwangton and Kwangsi), and were named the Hundred (Pai) Yueh before the Han Dynasty (206 B.C – 220 A.D.) due to the great diversity of local cultures. Not very much Yueh history has been available from Chinese history (of the Central Plains) apart from battles between Yueh and Wu during the Spring and Autumn Warring States Period, and the dispersion of part of the Yueh peoples to the north during the Han Dynasty, since in Chinese history populations other than those of the Central Plains have considered as “barbarians” (17, 19). The Minnan (Min) were one of the ethnic groups among the Yueh who lived in Fuchien, and according to Lin (17) and Meacham (19) the present-day Minnan are descendants of indigenous Minnan peoples although probably limited gene flow from the northern Han occurred during the Chin and Han Dynasties and also during the following several centuries, due to invasions of nomads from Mongolia in the north which caused internal migration from north to south (17). As the barbarian status of the Yueh gradually disappeared and they were finally given Han status in history, thus probably resulting in misinterpretation and erroneous self-assertion of present-day Minnan as “pure” descendants of the northern Han. In Chinese history, many ethnic minorities adopted Han culture, and many peoples from these ethnic groups often announced that they were Han, most likely because the Han culture was more dominant at that time and so being a member of a Han ethnic group was both beneficial and a source of pride in the past (17, 19, 20). This also imply to Hakka, as during South Song Dynasty (1127 – 1279 A.D.) or even earlier there were limited immigrants from Central Plains to southeast region of China. These peoples with their dominant Han culture influenced culturally and linguistically the indigenous Yueh peoples especially those who live in Kwangton. Subsequently few initial immigrants and the vast majority of indigenous Yueh peoples forming the Hakka ethnic group.

Two phylogenetic trees constructed by calculation of the genetic distances D and DA showed a slight difference in the order of clustering among southern Asians. The D tree appears to better fit into the history of “Taiwanese”, Thai-Chinese and Singapore Chinese, since they originated from the same area of the southeast coast of China but migrated to different places during the last few centuries. However, the trees constructed both by D and DA separated the southern Asian populations, including “Taiwanese”, from northern Han. Correspondence analysis of “Taiwanese” and many other populations also showed that there was a clear separation between the “Taiwanese” and northern Han. A phylogenetic tree constructed by HLA gene frequencies on marrow donors also showed that” Taiwanese” (Minnan and Hakka) clustering together with the southern Han are separated from the northern Han (8). Many other studies including HLA as well as other genetic markers such as immunoglobulins (22), blood groups (23), glucose-6-phosphate dehydrogenase (24) and microsatellites (25) also clearly separate the southern Han from the northern Han. A study on Chinese surnames and genetic differences between north and south China also separated southern Han from the northern Han (20). In that study, the southern Han cluster can be further subdivide into three subclusters: the lower Yangtze river centering around Shanghai; most of the Yangtze river basin; and the southeast coastal areas and islands off the coast (including Taiwan). Chinese surnames have a history of probably more than 4,000 years and are transmitted via the male line and can thus be considered as a Y-chromosome gene. The finding of southeast coastal subdivisions of the southern Han corresponds well with the history and populations of the Yueh. Also in that study, the map of the first two principal coordinates calculated by the gene frequencies for ABO, MN, and Rh(D) of 28 provinces of China plus Taiwan, it was revealed that there was a clear split between the populations of Taiwan and the southeast coastal provinces from all other parts of China, suggesting that “Taiwanese” and its originating southeast coastal populations (Yueh peoples) might be genetically distinct from the others.

These genetic data indicate that the southern Han are basically of southern origin and remain genetically distinct from the northern Han. “Taiwanese” who are descendants of the ancient Yueh peoples preserve the ancestral HLA haplotype A33-Cw10-B58-DRB1*03-DQB1*02 of the Yueh. The genetic distance between “Taiwanese” and southern Han warrant further study because half of the population samples contributing to the HLA data of southern Han used in this study were from Fuchien (5).

Yue Peoples

Map of Asia, 200 BC: Nan-Yue and Min-Yue

Yue (越,粵,鉞; Vietnamese: Việt; also seen as Yueh or Yuet) refers to ancient semi-Sinicized or non-Sinicized peoples of southern China, originally those along the eastern coastline of present-day Zhejiang province. In archaic Chinese, a number of characters (越,粵,鉞) were often used interchangeably to represent the same meaning

In ancient times, the northern Han Chinese referred to the peoples to their south collectively as the Yue. Historian Luo Xianglin has suggested that these peoples shared a common ancestry with the Xia Dynasty.

There is little evidence, however, that the Yue peoples held any common identity. The Yue people were not a single, united ethnic group although they are often mislabeled as such today.Historical texts often refer to the Hundred Yue tribes (百越). There is little evidence, however, that the Yue peoples held any common identity. The "Treatise of Geography" in Han Shu notes: "In the seven or eight thousand li from Jiaozhi to Kuaiji (modern southern Jiangsu or northern Zhejiang) the Hundred Yue are everywhere, each with their own clans." Just as the term Celt was used by the Greeks to describe what they perceived to be a broad cultural group, so the term Yue was a culturally relative term for the ancient Chinese.

From the Ninth century BC, two northern Yue peoples, the Gou-Wu and Yu-Yue, were increasingly influenced by their Chinese neighbours to their north. These two states were based in the areas of what is now southern Jiangsu and northern Zhejiang respectively. Their aristocratic elite learned the written Chinese language and adopted Chinese political institutions and military technology. Traditional accounts attribute the cultural change to the Grand Earl of Wu (吳太伯), a Zhou prince who had fled to the south. The marshy lands of the south gave Gou-Wu and Yu-Yue unique characteristics. They did not engage in extensive agrarian agriculture, relying instead more heavily on aquaculture. Water transport was paramount in the south, so the two states became advanced in shipbuilding and developed riverine warfare technology. They were also known for their fine swords.

In the Spring and Autumn Period, the two states, now called Wu and Yue, were becoming increasingly involved in Chinese politics. In 512 BC, Wu launched a large expedition against the large state of Chu, based in the Middle Yangtze River. A similar campaign in 506 succeeded in sacking the Chu capital Ying. Also in that year, war broke out between Wu and Yue and continued with breaks for the next three decades. In 473 BC, the Yue king Goujian finally conquered Wu and was acknowledged by the northern states of Qi and Jin. In 333 BC, Yue was in turn conquered by Chu. The Kings of the state of Yue, and therefore its succesor state Minyue, claimed to be descended from Yu the Great of the Chinese Xia dynasty. According to Sima Qian, Wu was founded by Wu Taibo, a brother of zhou wu wang, the King of the chinese Zhou dynasty.

After the unification of China by Qin Shi Huang, it became incorporated into the Chinese empire. The Qin armies also advanced south along the Xiang River to modern Guangdong and set up commanderies along the main communication routes. Throughout the Han Dynasty period two groups of Yue were identified, that of the Nan-Yue (南越) in the far south, who lived mainly in the area of what is now Guangdong, Guangxi, and Vietnam; and that of the Min-Yue (閩越) who lay to the southeast, centred on the Min River in modern Fujian. The Kings of Minyue claimed to be descended from Yu the Great of the Chinese Xia dynasty.

Sinification of these peoples was brought about by a combination of imperial military power, regular settlement and Chinese refugees. The difficulty of logistics and the malarial climate in the south made the displacement and eventual sinification of the Yue peoples a slow process. When the Chinese came into contact with local Yue peoples, they often wrested control of territory from them or subjugated them by force. When a serious rebellion broke out in 40 AD by the Trung Sisters in what is now modern Vietnam, a force of some 10,000 imperial troops was dispatched under General Ma Yuan. Between 100 and 184 no less than seven outbreaks of violence took place, often calling for strong defensive action by the Chinese.

As Chinese migrants gradually increased, the Yue were gradually forced into poorer land on the hills and in the mountains. Unlike the nomadic peoples of Central Asia, such as the Xiongnu or the Xianbei, however, the Yue peoples never posed any serious threat to Chinese expansion or control. Sometimes they staged small scale raids or attacks on Chinese settlements - termed "rebellions" by traditional historians. The Chinese for their part regarded them as being highly uncivilised and prone to fight one another.

While most Yue peoples were eventually assimilated into Han Chinese culture, the Kam-Tai (Daic): Zhuang, Buyi, Dai, Sui (Shui), Kam (Dong), Hlai (Li), Mulam, Maonan, Ong-Be (Lingao), Thai, Lao, Shan and the Vietnamese people retained their ethnic identity. The Vietnamese people eventually broke free from Chinese rule in the10th century and have their own state to this day.

The impact of Yue culture on Chinese culture has not been determined authoritatively but it is clear that it is significant. The languages of the ancient states of Wu (吳) and Yue form the basis the modern Wu language and to some extent the Min languages of Fujian. Linguistic anthropologists have also determined that a number of Chinese words can be traced to ancient Yue words. An example is the word "jiang" (江), meaning river. To some extent, some remnants of the Yue peoples and their culture can also be seen in some minority groups of China and the Vietnamese people retain the identity.

In modern Chinese, the characters of "越" and "粵" (both yuè) are differentiated. The former is used to refer to the original territory of the Yue Kingdom, the area of what is now northern Zhejiang, southern Jiangsu, and Shanghai, especially the areas around Shaoxing and Ningbo. The opera of Zhejiang, for example, is called "Yue Opera" (yueju, 越劇). The first character "越" is also associated with Vietnam. The second character "粵" (yuè) is associated with the southern province of Guangdong. Popularly called "Cantonese", both the standard form and regional dialects of the Yue language are spoken in Guangdong, Guangxi, Hong Kong, Macau and in many Cantonese communities around the world.

* HLA-B*5801 Allele as a Genetic Marker for Severe Cutaneous Adverse Reactions Caused by Allopurinol by Hung SI, Chung WH, Liou LB, Chu CC, Lin M, et. al.

Abstract: Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol-SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol-SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) (P < 10(-7)). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P value = 4.7 x 10(-24)] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23-6665.26); corrected P value = 8.1 x 10(-18)]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.

* Taiwan Experience Suggests that RhD Typing for Blood Transfusion Is Unnecessary in Southeast Asian Populations by Lin M

BACKGROUND: The high frequency of RhD (D) antigen among Taiwanese persons (99.67%) often imposes unnecessary risks of under-transfusion on D- patients awaiting D- blood. Also because of the rare occurrence of anti-D among Taiwanese persons, routine pretransfusion D typing has been discontinued in the Mackay Memorial Hospital since 1988. This report is the retrospective evaluation of the outcome of abolishing RhD typing for Taiwanese. STUDY DESIGN AND METHODS: More than 10 years of alloantibody data at Mackay Memorial Hospital Blood Bank were reviewed. The cases with anti-D were further used to analyze the potency of D antigen and to observe whether there were differences in the incidence of anti-D before and after discontinuation of routine D typing among Taiwanese individuals. RESULTS: The incidence of anti-D before and after discontinuation of routine pretransfusion D typing has remained unchanged. The immunogenicity of D and "Mi(a)" in Taiwanese persons is found to be similar. In terms of opportunity for immunization, however, the "Mi(a)" antigen (phenotype frequency 7.3% in Taiwanese persons) has become the most important blood group antigen in Taiwan. CONCLUSION: The results strongly support the exclusion of D typing from routine compatibility testing for individuals of Taiwanese origin. Because the low incidence of D- and relatively high incidence of "Mi(a)"+ phenotypes are common findings throughout southeast Asia, and because a population genetic study revealed that the Taiwanese people are genetically related to southern Asian populations, it is suggested that RhD typing for blood transfusion is unnecessary among southeast Asian populations.

* Association of HLA Class I With Severe Acute Respiratory Syndrome Coronavirus Infection by Lin M, et al.

BACKGROUND: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. METHODS: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. RESULTS: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). CONCLUSIONS: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.

* CTLA-4 Gene and Susceptibility to Human Papillomavirus-16-associated Aervical Squamous Cell Carcinoma in Taiwanese Women by Su TH, Chang TY, Lee YJ, Chen CK, Liu HF, Chu CC, Lin M, et al.

Abstract: Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer. The host immunogenetic background plays an important role in the persistence of HPV infection and subsequent development of cervical cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed mainly on activated T cells and is important in the down-regulation of T-cell activation. The aim of this study was to determine if polymorphisms of the CTLA-4 gene are associated with HPV-induced cervical cancer in Taiwanese women. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype -318 C/T, +49 A/G and CT60 A/G polymorphisms in 144 women with cervical squamous cell carcinoma (CSCC) and 378 ethnicity-matched healthy control women. The presence and genotypes of HPV in CSCC were determined by E6-, E7-based nested polymerase chain reaction. The frequency of C/T genotype of -318 C/T polymorphism was significantly higher in patients with HPV-16-positive CSCC compared with controls (odds ratio = 1.99, 95% confidence interval = 1.16-3.42, P(c) = 0.03). No significant associations were found for +49 A/G and CT60 A/G polymorphisms. Analysis of haplotypes, computationally inferred from genotype data, also revealed no significant differences in distribution among all subjects with CSCC, those with HPV-16-positive CSCC and controls. Our results suggest that the -318 C/T variant in the promoter region of the CTLA-4 gene is associated with HPV-16-associated CSCC in Taiwanese women.

* Influence of HLA-DRB1 Genes and the Shared Epitope on Genetic Susceptibility to Rheumatoid Arthritis in Taiwanese by Liu SC, Chang TY, Lee YJ, Chu CC, Lin M, et al.

OBJECTIVE: To investigate the association of predisposing and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in a Taiwanese population. METHODS: A total of 273 patients with RA and 480 healthy controls, all of Taiwanese origin, were genotyped for HLA-DRB1 alleles by polymerase chain reaction and sequence-based typing assays. The associations between RA and HLA-DRB1 alleles and genotypes were investigated by chi-squared test. RESULTS: The DRB1*0405 and *1001 phenotypes showed the most significant associations with RA (OR 4.04, 95% CI 2.84-5.77, pc = 3.2 10(-14); OR 5.25, 95% CI 2.10-13.06, pc = 3.0 10(-3), respectively). Individuals carrying single or double doses of the shared epitope (SE/non-SE or SE/SE) had higher risks of RA. The compound heterozygote of DRB1*0405/*1001 showed the largest increase in RA risk (OR 15.8, 95% CI 2.48-100.7, pc = 0.004). Single or double doses of SE alleles were significantly associated with a higher bone erosion rate. Rheumatoid factor positivity and bone erosion were more frequent in patients with at least one copy of DRB1*0405. CONCLUSION: Our results show that SE-encoding HLA-DRB1*0405 and *1001 are associated with RA in a Taiwanese population; this is the first time DRB1*1001 has been described in persons of Asian ethnicity. Heterozygotes of DRB1*0405 and *1001 predicted the strongest susceptibility to RA, suggesting that this genotype enhances susceptibility to RA in Taiwanese.

* 非原住民台灣人的基因結構 by 林媽利

The Liberty Times: 從基因的結構上，台灣人分少數的台灣原住民及大多數的非原住民台灣人，台灣原住民在台灣島內經過幾千年長期的隔離，形成相似及一致的基因結構。非原住民的台灣人是由多個族群融合而形成，因此基因結構多樣及互異。我們共分析一百名非原住民台灣人的體染色體組織抗原、母系血緣及父系血緣，試著探討台灣人與周圍族群的關係，也就是與台灣原住民、東南亞島嶼族群（印尼、菲律賓）、中國的福建廣東及亞洲大陸的關係。這一百人中有十九人的近代祖先來自福建廣東，三人的祖父來自其他省份，沒外國祖先。

組織抗原及許多體染色體基因的研究，可從建構族群關係樹測定族群間親緣的遠近關係，可惜這關係樹看不清楚混血的情形。然而我們成功的比對了福建人與台灣人間共有組織抗原半套型的情形，發現台灣人的半套型基因有四十八％是來自福建，其他五十二％主要來自原住民、東南亞島嶼族群及少數的可能來自歐洲、日本、東北亞、印度及西藏。母系血緣是粒線體ＤＮＡ的序列在複製時發生錯誤的複製（突變），新的突變傳下去形成新的母系血緣，母系血緣是經母親的卵子傳給女兒及兒子，再經由女兒的卵子傳到下一代，精子的粒線體並不進去受精卵，所以女性的粒線體ＤＮＡ代表母系的血緣。Ｙ染色體上ＤＮＡ的突變形成父系血緣。母系血緣的研究遠較父系血緣多，所以母系血緣的型別多樣，讓台灣原住民的母系血緣可以很清楚的和亞洲大陸的血緣區分。

我們的研究顯示台灣原住民與東南亞島嶼族群（印尼及菲律賓等）在血緣上很接近，不易區分，而且顯示台灣原住民在上萬年之間陸續來自東南亞島嶼，其間兩地部分族群可能有相互遷移。我們用這二大族群的母系血緣與一百個台灣人比對，結果發現台灣人的母系血緣有四十七％屬於台灣原住民及東南亞島嶼的族群，四十八％屬於亞洲大陸，還有五％屬於日本的母系血緣。父系血緣雖不像母系血緣可以清楚的區分亞洲島嶼與亞洲大陸的血緣，但這一百人中的五十八名男性可歸類為四十一％的父系血緣來自台灣原住民及東南亞島嶼族群，五十九％的父系血緣來自亞洲大陸。從以上三個基因系統看到台灣人的基因有多方不同族群的來源，有台灣原住民、東南亞島嶼、中國東南沿海及亞洲大陸，還有意想不到的少數日本人及白種人。

台灣人的基因結構根據體染色體組織抗原，母系血緣及父系血緣三個不同系統的分析得到相當接近的結果，就是台灣人的基因大概一半來自台灣原住民及東南亞島嶼族群，另一半來自福建廣東及亞洲大陸。歷史上唐山公的故事可從台灣人有五十九％亞洲大陸的父系血緣得到印證，至於平埔嬤在歷史上的重要性還是很清楚的看到，之後唐山嬤的大舉遷台建構了另一半的母系血緣。母系血緣是看外祖母的血緣，父系血緣是看內祖父的血緣，從組織抗原可以看到外祖父及內祖母的血緣，在一百人當中只有三十三人的父母系血緣全部來自亞洲大陸，其他六十七人的父母系血緣是混合了台灣原住民、東南亞島嶼族群及亞洲大陸的血緣。分析這三十三人的組織抗原半套型的來源，看到十八人帶有台灣原住民的基因，十人帶有中國東南沿海越族特徵的基因，二個西南亞洲基因及各一個北方漢人、藏人及歐洲人的基因，所以根據三個系統的分析，八十五％的台灣人是帶有台灣原住民的血緣，所以是平埔公、平埔嬤、唐山公、唐山嬤，還有高山公、高山嬤及少數外國基因一起建構了非原住民台灣人的基因。

* 原住民基因解密 by 林媽利

Excerpt: 我們共研究六四○名台灣高山原住民的mtDNA（粒腺體ＤＮＡ），藉著測定不同的突變而歸納出不同的mtDNA型，再測定不同型發生的年代，來推測台灣原住民的祖先來處。

結果發現，台灣原住民雖與亞洲大陸有遠古以前的關係，卻有自己獨特的mtDNA型，推測形成年代介於距今七七○○年到一萬六一○○年前，因此可推測在一萬一○○○年前冰河時期終結，海水上升，台灣變成島嶼的前後時間，在台灣形成了這些mtDNA型，而成為台灣原住民獨特的標誌。顯示台灣原住民與亞洲大陸的族群在冰河時期結束時即已分開。

在台灣原住民看到的幾個主要mtDNA型，在東南亞島嶼上也以高頻率出現，顯示台灣原住民很可能是從東南亞島嶼遷移過來的。

* Diversity of HLA Among Taiwan's Indigenous Tribes and the Ivatans in the Philippines by Chu CC, Lin M, et al.

Abstract: Taiwan's indigenous tribes, especially the east coast tribes are not only closely related to Oceania but also with the Australian aborigines. The Ivatans of the Batan Islands in the Philippines are closely related to the Yami tribe of Taiwan as cultural and anthropological studies have shown. Many DRB1 alleles (*15021, *16021, *0404, *04051, *11011, *12021, *1401, *08032) have high allele frequencies (>20%) in certain tribes, suggesting Taiwan's indigenous tribes are homogeneous populations. These high frequency DRB1 alleles and also some HLA-A-B-DR haplotypes found in Taiwan's indigenous tribes are also found in Oceania, Australian aborigines, south and north east Asians and American Indians, lending further support to our previous findings that Taiwan's indigenous tribes are more or less genetically related to both northern and southern Asians, possibly as well as Amerindians. HLA-A*2402 with a remarkably high frequency among Taiwan's indigenous tribes (52.1% approximately 86.3%), especially the central mountain tribes, possibly represents not only founder effects and population bottlenecks, but also positive selection of the allele. Although the Ami tribe has the highest ever reported frequencies of the DRB1*0404 and DRB1*0405, these alleles have not been found to be associated with rheumatoid arthritis as previously described for Caucasians. In addition, DRB1*1401 has a high frequency in most tribes but is not associated with psoriasis as previously indicated in some studies, suggesting the involvement of some additional genetic and/or environmental factors mechanism in the development of these diseases.

* Heterogeneity of Taiwan’s Indigenous Population: Possible relation to prehistoric Mongoloid dispersals by M. Lin, et al.

Abstract: Taiwan's 9 indigenous tribes (Tsou, Bunun, Rukai, Atayal, Saisiat, Ami, Puyuma, Yami, Paiwan) are highly homogeneous within each tribe, but diversified among the different tribes due to long-term isolation, most probably since Taiwan became an island about 12,000 years ago. Homogeneity of each tribe is evidenced by many HLA-A,B,C alleles having the world's highest ever reported frequencies, e.g. A24 (86.3%), A26 (18.8%), Cw10 (36.8%), Cw7 (66%), Cw8 (32.1%), B13 (27.9%), B62 (37.4%), B75 (18%), B39 (53.5%), B60 (33.3%), and B48 (24%). Also, all of these tribes have HLA class I haplotype frequencies greater than 10%, with A24-Cw7-B39 in Saisiat (44.5%) being the highest, suggesting Taiwan's indigenous tribes are probably the most homogeneous ( the "purest") population in the world. A24-Cw8-B48, A24-Cw10-B60 and A24-Cw9-B61 found common to many Taiwan indigenous tribes, have also been observed in Maori, Papua New Guinea Highlanders, Orochons, Mongolians, Inuit, Japanese, Man, Buryat, Yakut, Tlingit, Tibetans and Thais. These findings suggest Taiwan's indigenous groups are more or less genetically related to both northern and southern Asians. Principal component analysis and the phylogenetic tree (using the neighbor-joining method) showed close relationship between the indigenous groups and Oceanians. This relationship supports the hypothesis that Taiwan was probably on the route of prehistoric Mongoloid dispersals that most likely took place along the coastal lowland of the Asian continent (which is under the sea today). Cultural anthropology also suggests a relationship between Taiwan's indigenous tribes and southern Asians and to a lesser extent, northern Asians. However, the indigenous groups show little genetic relationship to current southern and northern Han Chinese.

* Immunoglobulin Allotypes among Taiwan Aborigines: Evidence of malarial selection could affect studies of population affinity by Moses S. Schanfield, Koji Ohkura, Marie Lin, et al.

Abstract: The aborigines of Taiwan represent the indigenous inhabitants of the island at the time of the arrival of the Chinese from the mainland. Linguistically, the aboriginal Taiwanese are related to the Malayo-Polynesian-speaking inhabitants of Indonesia and the Philippines. Three tribes occupied lowland areas while six tribes occupied highland areas. Previous studies indicate that genetic markers associated with malaria occur in lowland populations. Though the GM haplotypes are demonstrated to be very useful in the measure of population affinities, the possibility of malarial selection on this locus could affect studies of population affinity. The present work is a case study to see whether a subdivided insular population under a possible selective load will provide divergent clustering analysis depending on the population sampled. Immunoglobulin allotype (GM and KM) profiles were generated on 230 lowland and 407 highland Taiwan Aborigines from the nine tribes. A highly significant difference in GM haplotype distribution was detected between lowland and highland populations (adjusted G = 69.408, 2 df [degrees of freedom], p < 0.00001). There were no significant differences in KM*1 frequency by altitude. The Taiwan Aboriginal GM and KM frequencies were compared to data from Indonesians, Vietnamese, Thai, Malay, Chinese from Taiwan, and Ryukyu Islanders from Okinawa using cluster analysis. The lowland populations plot among the Thai (N, NC) and Malayan Aborigines. In contrast, the highland and total Taiwan Aborigine samples plot with the Indonesian, Vietnamese, and Malayan Negrito samples. Thus, depending on the populations of Taiwan Aborigines used, different conclusions could be reached. The highland population supports the published linguistic ties; however, the lowland population does not support the linguistic relationship with Indonesian populations but is more closely related to Thai and Malays, or reflects a similar selection history.

* Population Study of Polymorphic Microsatellite DNA in Taiwan by James Chun-I Lee, Marie Lin, et al.

Abstract: This study examined the population frequency and genetic diversity of 13 autosomal STR loci in 12 populations of Taiwanese. The populations included Bunun, Paiwan, Saisiat, Tao, Ami, Rukai, Atayal, Tsou, Pazeh, Puyumar, Hakka and Han. The STR loci were the CODIS including D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, TH01, TPOX and CSF1PO. In this study no deviations from the Hardy-Weinberg equilibrium were observed for the 13 STR loci by the exact test. The range of matching probability for the 13 loci is from 1.44 × 10-13 in Tsou to 8.76 × 10-15 in Taiwanese Han population. Only one mutation event in D8S1179 locus, altering allele 16 to 15, was detected in 250 meiosis alleles in the mutation screening. The Neighbor-joining tree of cluster analysis was constructed with the genetic distance of 12 populations on 13 loci, which may be useful for phylogenetic study of populations in Taiwan. These data supported the Hanization hypothesis for populations in Taiwan.

* Traces of Archaic Mitochondrial Lineages Persist in Austronesian-Speaking Formosan Populations by Jean A Trejaut, Toomas Kivisild, Jun Hun Loo, Chien Liang Lee, Chun Lin He, Chia Jung Hsu, Zheng Yuan Li,and Marie Lin

Abstract: Genetic affinities between aboriginal Taiwanese and populations from Oceania and Southeast Asia have previously been explored through analyses of mitochondrial DNA (mtDNA), Y chromosomal DNA, and human leukocyte antigen loci. Recent genetic studies have supported the “slow boat” and “entangled bank” models according to which the Polynesian migration can be seen as an expansion from Melanesia without any major direct genetic thread leading back to its initiation from Taiwan. We assessed mtDNA variation in 640 individuals from nine tribes of the central mountain ranges and east coast regions of Taiwan. In contrast to the Han populations, the tribes showed a low frequency of haplogroups D4 and G, and an absence of haplogroups A, C, Z, M9, and M10. Also, more than 85% of the maternal lineages were nested within haplogroups B4, B5a, F1a, F3b, E, and M7. Although indicating a common origin of the populations of insular Southeast Asia and Oceania, most mtDNA lineages in Taiwanese aboriginal populations are grouped separately from those found in China and the Taiwan general (Han) population, suggesting a prevalence in the Taiwanese aboriginal gene pool of its initial late Pleistocene settlers. Interestingly, from complete mtDNA sequencing information, most B4a lineages were associated with three coding region substitutions, defining a new subclade, B4a1a, that endorses the origin of Polynesian migration from Taiwan. Coalescence times of B4a1a were 13.2 ± 3.8 thousand years (or 9.3 ± 2.5 thousand years in Papuans and Polynesians). Considering the lack of a common specific Y chromosomal element shared by the Taiwanese aboriginals and Polynesians, the mtDNA evidence provided here is also consistent with the suggestion that the proto-Oceanic societies would have been mainly matrilocal.

* Climate Change and Postglacial Human Dispersals in Southeast Asia by Pedro Soares, Jean Alain Trejaut, Jun-Hun Loo, Catherine Hill, Maru Mormina, Chien-Liang Lee, Yao-Ming Chen, Georgi Hudjashov, Peter Forster, Vincent Macaulay, David Bulbeck, Stephen Oppenheimer, Marie Lin, et. al.

Abstract: Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years—in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000–7,000 years ago, were the main forces shaping modern human diversity in the region.

* Philippine Mitochondrial DNA Diversity: A populated viaduct between Taiwan and Indonesia? by Kristina A. Tabbada, Jean Trejaut, Jun-Hun Loo, Yao-Ming Chen, Marie Lin, et al.

Abstract: Relatively little is known about the genetic diversity of the Philippine population, and this is an important gap in our understanding of Southeast Asian and Oceanic prehistory. Here we describe mtDNA variation in 423 Philippine samples and analyze them in the context of the genetic diversity of other Southeast Asian populations. The majority of Philippine mtDNA types are shared with Taiwanese aboriginal groups and belong to haplogroups of post-glacial and pre-Neolithic origin which have previously been identified in East Asian and Island Southeast Asian populations. Analysis of Hypervariable Segment I sequence variation within individual mtDNA haplogroups indicates a general decrease in the diversity of the most frequent types (B4a1a, E1a1a, M7c3c) from the Taiwanese aborigines to the Philippines and Sulawesi, although calculated standard error measures overlap for these populations. This finding, together with the geographical distribution of ancestral and derived haplotypes of the B4a1a sub-clade including the Polynesian Motif, is consistent with southward dispersal of these lineages "Out of Taiwan" via the Philippines to Near Oceania and Polynesia. In addition to the mtDNA components shared with Taiwanese aborigines, complete sequence analyses revealed a minority of lineages in the Philippines which share their origins - possibly dating back to the Paleolithic - with haplogroups from Indonesia and New Guinea. Other rare lineages in the Philippines have no closely related types yet identified elsewhere.

* More Genetic Sharing among the Populations of Taiwan than Expected: A Plain Tribes (Pinpu) Perspective
by Marie Lin, et al.

Conclusion: Autosomal recombining HLA and non-recombining haploid systems (mtDNA and NRY) of Taiwan present-day populations revealed that plain tribes shared their genes with TwA, ISEA and CSEA, and appear more distant from CA.

Using ancient bone remains from Taiwan plain tribe burial sites, and studying non-recombining maternal mtDNA system, it was shown that the CSEA and CA genetic heritage of the Taiwan plain tribes was not only acquired during the past 400 years from people of the southeast coast of China (current belief), but may have been acquired as far back as 4000 years ago from ancient prehistoric sailing agriculturist migrants (the broad genetic structure in those days was similar to that seen in CSEA today). Older bone remains will be needed to demonstrate older migration, but most importantly these preliminary results will need further analysis in the future. Caution will have to be taken as it is usual to label haplogroups that are not seen among TwA as genetic markers of recent continental origin, here, on the contrary, our results show that the presence of these same haplogroups have arrived much earlier and may actually help to reconstruct the genetic make up of descendants of prehistoric migrants from continental Asia a few thousand years ago.

The Mitochondrial DNA analysis revealed two genetic "Aboriginalities" within the plain tribes, one already well defined set of haplogroups shared with mountain tribe Aborigines (TwA) (and ISEA), and the other set of haplogroups shared between plain tribes Aborigines and CSEA. The arrival time of the latter set of haplogroups could be traced back to several thousand years prior the commonly accepted period of 400 years.

We showed that the genetic make up of the plain tribes today, most likely, contains an older Taiwan heritage than previously thought. This study also support our previous findings describing that 95% of Siraya carried at least one gene of TwA origin (or gene also seen in TwA and ISEA), and Pazeh 89%. Finally, when confirmed these resulted, may have strong implication in drawing new hypothesis about the historical demography of present day Taiwanese.

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如果我們無法超越過去的不幸，就看不到海闊天空的美麗及欣賞路邊小花的美麗。

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風中的波斯菊 -林媽利的生命故事 by 劉湘吟