Fong-Ming Chang

The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus.

Abstract The dopamine D4 receptor gene (DRD4) has an expressed polymorphism in the third exon that may have functional relevance. The polymorphism exists at two levels. At the higher level there is an imperfect tandem repeat of 48 base pairs (bp) coding for 16 amino acids; alleles have been identified with 2 (32 amino acids) to 10 (160 amino acids) repeats. The imperfect nature of the repeats is responsible for a more subtle level of variation since alleles with the same number of repeats can differ in the exact sequences or in the order of the variants of the 48-bp unit. We have undertaken a global survey of this expressed polymorphism as one approach to understanding the evolutionary significance and origins of the polymorphism as well as understanding what selective forces, if any, may be operating at this locus. As the first step, we have determined the repeat number genotype of the DRD4 repeat polymorphism in 1,327 individuals from 36 different populations. The allele frequencies differ considerably among the different populations. The 4-repeat allele was the most prevalent (global mean allele frequency = 64.3%) and appeared in every population with a frequency ranging from 0.16 to 0.96. The 7-repeat allele was the second most common (global mean = 20.6%), appearing quite frequently in the Americas (mean frequency = 48.3%) but only occasionally in East and South Asia (mean frequency = 1.9%). The 2-repeat allele was the third most common (global mean frequency = 8.2%) and was quite frequent in East and South Asia (mean frequency = 18.1%) while uncommon in the Americas (mean frequency = 2.9%) and Africa (mean frequency = 1.7%). The universality of the polymorphism with only three common repeat-number alleles (4, 7, and 2) indicates that the polymorphism is ancient and arose before the global dispersion of modern humans. The diversity of actual allele frequencies for this expressed polymorphism among different populations emphasizes the importance of population considerations in the design and interpretation of any association studies carried out with this polymorphism.

Three-Dimensional Ultrasound-Assessed Fetal Thigh Volumetry in Predicting Birth Weight

Objective To compare the accuracy of three-dimensional ultrasound-assessed fetal thigh volumetry in predicting birth weight with that of other commonly used formulas composed of biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) by two-dimensional ultrasound. Methods We assessed the thigh volume of 100 fetuses using three-dimensional ultrasound. Meanwhile, their BPD, AC, and FL were measured by two-dimensional ultrasound. All infants were delivered within 48 hours after the ultrasound examinations. From polynomial regression analysis, we generated a best-fit formula for the thigh volume to predict birth weight. The accuracy of this thigh-volume formula was compared with those of three formulas commonly used in the United States. In addition, another group of 50 fetuses was measured for prospective validation. Results The thigh volume assessed by three-dimensional ultrasound was highly correlated with birth weight (r = 0.89, n = 100, P < .0001). The best-fit formula for thigh volume to predict birth weight was linear, and it was superior to the other commonly used two-dimensional formulas in predicting birth weight. The predicting error (0 g), percent error (0.7%), absolute error (176.1 g), and absolute percent error (5.8%) of the thigh-volume formula were all smaller than those of the other formulas (n = 100, all P < .05). In addition, the thigh-volume formula predicted birth weight more accurately than the other two-dimensional formulas in the prospective-validation group. The three-dimensional formula had smaller mean values of predicting error (38.6 g), percent error (1.5%), absolute error (160.0 g), and absolute percent error (5.1%) than the two-dimensional formulas (n = 50, all P ≤ .001), as well as the smallest variances of the above errors (178.1 g, 5.6%, 84.3 g, and 2.9%, respectively). Conclusion The three-dimensional ultrasound-assessed thigh volume has better accuracy in predicting birth weight than the commonly used formulas by two-dimensional ultrasound, and it may improve fetal weight prediction in clinical practice. However, a large-scale prospective validation study may be needed to confirm our conclusions.

Predicting birth weight by fetal upper-arm volume with use of three-dimensional ultrasonography.

OBJECTIVE Our purpose was to determine the usefulness and accuracy of the three-dimensional ultrasonography assessed fetal upper-arm volume in predicting birth weight. STUDY DESIGN From June 1996 to October 1996, we performed a prospective study of ultrasonography on 105 pregnant women without fetal structural anomaly or aneuploidy. Both the traditional two-dimensional ultrasonographic parameters and three-dimensional ultrasonography for fetal upper arm volume were measured within 48 hours of delivery. RESULTS The upper arm volume correlated well with birth weight (r = 0.92, n = 105, p < 0.0001). With use of linear and polynomial regression, we obtained a best-fit new formula, Birth weight = 1088.60 + 36.024 x Upper-arm volume. The accuracy of this new formula is compared with that of two Chinese equations predicting fetal weight reported before and other formulas commonly used in the world as well. Our formula is more accurate in predicting birth weight than all the other formulas by traditional two-dimensional ultrasonography, either in error, percentage error, or absolute error. Another group by prospective validation further proved this finding. CONCLUSION The upper-arm volume assessed by three-dimensional ultrasonography can accurately predict birth weight, and its accuracy is superior to the previous, formulas. Our study has at least validated the application of upper-arm volume by three-dimensional ultrasonography in estimating fetal weight. Further larger series are needed to confirm our findings.

THREE-DIMENSIONAL ULTRASOUND ASSESSMENT OF FETAL LIVER VOLUME IN NORMAL PREGNANCY: A COMPARISON OF REPRODUCIBILITY WITH TWO-DIMENSIONAL ULTRASOUND AND A SEARCH FOR A VOLUME CONSTANT

The purposes of this study are to compare the reproducibility of two-dimensional ultrasound (2DUS) and three-dimensional ultrasound (3DUS) in the assessment of fetal liver volume (LV), and to test whether the fetal LV assessed by the traditional method with 2DUS is equal to that with 3DUS in normal pregnancy. If significantly different, we then try to calculate a new constant of fetal LV for the traditional equation from the LV values obtained with 3DUS. In total, 30 normal singleton fetuses with gestational ages ranging from 20 to 30 weeks were included for the reproducibility test and 55 cases ranging from 20 to 31 weeks gestation were enrolled for finding a new volume constant of LV. The results showed that 3DUS is superior to 2DUS in the reproducibility test of fetal LV assessment. Moreover, the LV assessed with the traditional 2DUS method (identified as LV_42) was significantly smaller than that measured with 3DUS (P < 0.001). If the traditional 2DUS equation is to be used, the multiplying factor in the equation for the calculation of LV should be modified to 0.55 (SE = 0.017, N = 55). With the new volume constant, the new derived LV with 2DUS (identified as LV 55) was not different from that with 3DUS (identified as LV_3D). In conclusion, we recommend that 3DUS, instead of 2DUS, should be used for reaching an accurate assessment of fetal LV. Otherwise, applying our new volume constant may be of help in detecting abnormal fetal liver growth when only 2DUS is available.

Tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4).

The dopamine D4 receptor (DRD4) is a member of the D2-like dopamine receptor family. Polymorphisms at the DRD4 gene have been examined for association with a wide range of neuropsychiatric disorders and normal behavioral variation. The DRD4 gene is unusual in its high amount of expressed polymorphism in humans. Here we study the identification of a polymorphic tandem duplication of 120 bp located 1.2 kb upstream of the initiation codon. The duplicated region contains consensus sequences of binding sites for several known transcription factors, suggesting that different alleles may differ in their transcriptional activity. Because chimpanzees, gorillas, and orangutans lack the duplication, the duplicated allele is inferred to be derived. The frequency of this derived duplication allele ranges from 0.40-0.81 in the 11 populations from around the world typed for this polymorphism. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:705-709, 1999.

Assessment of fetal cerebellar volume using three-dimensional ultrasound.

The purposes of this study were to assess the fetal cerebellar volume during normal gestation using three-dimensional (3-D) ultrasound (US) and to establish a normal chart of fetal cerebellar volume using Altmans model of statistics. In total, 231 healthy fetuses were studied for assessment of cerebellar volume using a 3-D US volume scanner. The fetuses to be studied were selected to give a cross-sectional series (i.e., each fetus was examined only once). Polynomial regression analysis was calculated to find the best-fit model using gestational age as the independent variable and cerebellar volume as the dependent variable. Altmans model was used to calculate the age-related reference centiles for the variance of cerebellar volume. In addition, common fetal growth indices, such as biparietal diameter, occipitofrontal diameter, head circumference, abdominal circumference, femur length and estimated fetal weight, were also measured for the correlation between cerebellar volume and these indices. Our results indicated that the fetal cerebellar volume was highly correlated with gestational age in normal pregnancies with the best-fit polynomial regression equation of a second-order (r = 0.91, p < 0.0001). In addition, fetal cerebellar volume in normal gestation is also highly correlated with common fetal growth indices, such as biparietal diameter, occipitofrontal diameter, head circumference, abdominal circumference, femur length and estimated fetal weight (all p < 0.0001). Following the Altmans model, a normal growth chart of fetal cerebellar volume was established for clinical reference. In conclusion, with 3-D US, the assessment of fetal cerebellar volume becomes feasible. We believe that fetal cerebellar volume assessed by 3-D US may be useful in detecting cerebellar hypoplasia and relevant syndromes prenatally.

No association between alcoholism and multiple polymorphisms at the dopamine D2 receptor gene (DRD2) in three distinct Taiwanese populations

This study examined whether there is evidence for an association between alcoholism and the alleles of the TaqI A, TaqI B, and short tandem repeat polymorphisms (STRP), both individually and as haplotypes, at the dopamine D2 receptor gene (DRD2) in males of three populations from Taiwan. We studied 46 Chinese Han (21 alcoholics and 25 nonalcoholics), 42 Atayal (21 alcoholics and 21 nonalcoholics), and 40 Ami (20 alcoholics and 20 nonalcoholics). Alcoholism was diagnosed according to DSM-III-R criteria and all individuals in the alcoholic groups were severely affected. Significant linkage disequilibrium occurs for the three polymorphic sites in all three populations. No significant association was observed between any of the three polymorphisms at the DRD2 locus, tested individually and as haplotypes, and alcoholism in the three subject groups. We conclude that no association exists between genetic variation at the DRD2 locus and alcoholism in Chinese Han, Atayal, and Ami males.

Three-dimensional ultrasound in the assessment of fetal cerebellar transverse and antero-posterior diameters.

Fetal cerebellum scanning by prenatal ultrasound (US) is very important for early detection of fetal central-nervous-system anomaly, as well as for the determination of gestational age (GA). Due to the small organ size and the unique shape of the fetal cerebellum (CL), accurate measurement of the dimensions of CL by two-dimensional (2-D) US is not easy if the appropriate plane cannot be reached. With the advent of three-dimensional (3-D) US, the disadvantages of 2-D US in assessing the fetal CL dimensions can be avoided. The purpose of this study was to assess the fetal cerebellar transverse diameter (CTD) and cerebellar antero-posterior diameter (CAD) using 3-D US. First, we compared the reproducibility of 2-D and 3-D US on the assessment of fetal cerebellar dimensions. Second, we prospectively measured CTD and CAD in 223 healthy fetuses using a cross-sectional design with an attempt to establish the normal growth charts of fetal CL. Our results showed 3-D US is superior to 2-D US in the reproducibility test of fetal cerebellar dimensions. In addition, with GA as the dependent variable, polynomial regression analysis showed that the best-fit equations for both CTD vs. GA and CAD vs. GA were the first-order. The best-fit predictive equation of GA by CTD was GA (week) = 9.0281 + 0. 58533 x CTD (mm) (r = 0.95, n = 223, SE = 1.82 weeks, p < 0.0001), and the best-fit predictive equation of GA by CAD was GA (week) = 10. 855 + 1.1672 x CAD (mm) (r = 0.82, n = 223, SE = 3.41 weeks, p < 0. 0001). Furthermore, all the correlation coefficients of CTD or CAD vs. the common fetal growth indexes were also highly significant (all p < 0.0001). In conclusion, our data of fetal CL dimensions assessed by 3-D US may serve as a useful reference in assessing fetal CL growth, dating GA or detecting fetal CL anomalies.

Ovarian stroma flow intensity decreases by age: a three-dimensional power doppler ultrasonographic study

This was a prospective comparative clinical study to test the hypothesis that the flow intensity of the ovarian stroma decreases in the order of the aging process. A total of 100 consecutive women who came to our outpatient clinic for Pap smear examination were recruited. They were divided into three groups. The premenopause group (58 women) had menstruated within the last 3 months and had normal ovaries (no polycystic ovary or any pathologic cyst or mass), as demonstrated on the baseline ultrasound (US) examination. The perimenopause group (20 women) had last menstruated between 3 and 12 months earlier and had normal ovaries. The postmenopause group (22 women) had had no menstrual cycle within the last 12 months and had normal ovaries. Three-dimensional power Doppler US was applied to quantify the blood flow and vascularization within the stroma of the bilateral ovaries. The results showed that the E2 level decreased in the order of: premenopause (mean +/- SD; 40.88 +/- 40.65 pg/mL), perimenopause (22.00 +/- 13.61 pg/mL), then postmenopause (17.25 +/- 16.40 pg/mL). The vascularization index (VI) (6.95 +/- 8.35; 1.11 +/- 0.93; 0.53 +/- 1.75; respectively), flow index (FI) (15.98 +/- 7.59; 12.00 +/- 3.86; 5.18 +/- 5.31; respectively) and vascularization-flow index (VFI) (1.25 +/- 1.59; 0.18 +/- 0.15; 0.09 +/- 0.32; respectively) all decreased significantly in the order of premenopause, perimenopause, then postmenopause. To the best of our knowledge, this is the first study using 3-D power Doppler sonography that proves that the flow intensity decreases along with the aging process in the ovarian stroma.

PRENATAL DIAGNOSIS OF CLEFT PALATE BY THREE-DIMENSIONAL ULTRASOUND

Prenatal diagnosis of cleft palate is very important to prenatal consultation and management after birth. To examine if three-dimensional (3-D) ultrasound (US) is an accurate diagnostic method for clinical use, we analyzed our experience in detecting cleft palate by 3-D US. From June 1996 to January 2000, 21 fetuses with facial clefts were scanned by 2-D US, as well as by 3-D US. The coronal and oblique planes were reconstructed by 3-D US to detect the cleft palate. In addition, level II US was performed to find any possibly associated anomalies. All the scans were recorded on optic disks for final analysis. In our study, the gestational age when prenatal diagnosis was made by US initially was between 20 and 34 weeks. The accuracy for prenatal diagnosis of cleft lip with or without cleft palate by 3-D US was 100%, which was superior to that by 2-D US (p < 0.05). In addition, we proposed a novel method to evaluate the cleft palate systemically by 3-D US. In conclusion, from our study, fetuses with cleft lip combined with or without cleft palate can be easily differentiated by 3-D US. The reconstruction of coronal and oblique planes by 3-D US is a powerful tool for detecting cleft palate.